BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metasta...BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.展开更多
In this editorial,we reviewed the article by Fadlallah et al that was recently published in the World Journal of Clinical Oncology.The article provided a comprehensive and in-depth view of the management and treatment...In this editorial,we reviewed the article by Fadlallah et al that was recently published in the World Journal of Clinical Oncology.The article provided a comprehensive and in-depth view of the management and treatment of colorectal cancer(CRC),one of the leading causes of cancer-related morbidity and mortality worldwide.The article analyzed the therapeutic modalities and their sequencing,focusing on total neoadjuvant therapy for locally advanced rectal cancer.It highlighted the role of immunotherapy in tumors with high microsatellite instability or deficient mismatch repair,addressing recent advances that have improved prognosis and therapeutic response in localized and metastatic CRC.Innovations in surgical techniques,advanced radiotherapy,and systemic agents targeting specific mutational profiles are also discussed,reflecting on how they revolutionized clinical management.Circulating tumor DNA has emerged as a promising tool for detecting minimal residual disease,prognosis,and therapeutic monitoring,solidifying its role in precision oncology.This review emphasized the importance of technological and therapeutic advancements in improving clinical outcomes and personalizing CRC treatment.展开更多
Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its wid...Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.展开更多
BACKGROUND Colorectal cancer(CRC)is a prevalent malignant neoplasm characterized by subtle early manifestations.AIM To investigate the correlation among serum lipid profiles,the triglyceride-glucose(TyG)index,and the ...BACKGROUND Colorectal cancer(CRC)is a prevalent malignant neoplasm characterized by subtle early manifestations.AIM To investigate the correlation among serum lipid profiles,the triglyceride-glucose(TyG)index,and the atherosclerotic index(AI)in patients with CRC.Furthermore,it explored the clinical diagnostic utility of combining serum lipids with cancer antigens in the context of CRC.METHODS A retrospective analysis encompassed 277 patients with CRC and 1034 healthy individuals.RESULTS Following propensity score matching,patients with CRC exhibited significantly reduced levels of serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol(LDL-C),as well as a diminished TyG index.Conversely,they displayed elevated AI levels compared to their healthy counterparts.Patients in advanced stages exhibited lower serum levels of TG,TC,and LDL-C compared to those in early stages.Patients with positive lymph node metastasis demonstrated reduced levels of TG,LDL-C,and the TyG index.Receiver operating characteristic analysis revealed that the combination of the TyG index,carcinoembryonic antigen,and carbohydrate antigen 19-9 yielded the highest positive prediction rate for CRC at 75.3%.CONCLUSION Preoperative serum lipid profiles exhibit a robust association with patients with CRC.The concurrent assessment of multiple serum lipids and cancer antigens effectively enhances the diagnostic accuracy for CRC.展开更多
In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology.Surgical resection for peritoneal metastases from colorectal cancer(CRC)has been gradually accepted in t...In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology.Surgical resection for peritoneal metastases from colorectal cancer(CRC)has been gradually accepted in the medical oncology community.A randomized trial(PRODIGE 7)on cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)failed to prove any benefit of oxaliplatin in the overall survival of patients with peritoneal metastases from colorectal origin.Nevertheless,isolated systemic chemotherapy for CRC stage IV has demonstrated a reduced response in peritoneal metastases than that obtained in other metastatic sites such as the liver.Another tool is required in those patients to achieve more local control of the disease.Surgical groups in peritoneal surgery continue to use HIPEC in their procedures,using other agents than oxaliplatin for peritoneal cavity infusion,such as mitomycin C.These patients present with complex surgical issues to manage,and consequently a large burden of complications has to be anticipated.Therefore,identifying patients who will benefit from CRS with or without HIPEC would be of great interest.展开更多
BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC patients.Although therapy may initially yield positive...BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC patients.Although therapy may initially yield positive results,the development of drug resistance can result in treatment failure and cancer recurrence.This resistance is often attributed to the presence of cancer stem cells(CSCs).These CSCs not only contribute to therapeutic resistance but also play crucial roles in the initiation and development of tumor metastasis.AIM To investigate the antitumor effects of SH-4-54,which are mediated by targeting CSCs relative to treatment outcomes.METHODS CSCs were enriched by culturing CRC cells in serum-free medium.Hallmarks of stemness and IL-6/JAK2/STAT3 signaling were detected by Western blotting.Indicators of CSC malignancy,including proliferation,invasion,and tumor formation,were measured.RESULTS In this study,we employed SH-4-54,which exhibits anticancer activity in solid tumors through targeting the SH2 domain of both the signal transducer and activator of transcription(STAT)3 and the STAT5,and evaluated its effects on stemness and chemoresistance in colorectal CSCs.As expected,SH-4-54 treatment inhibited the phosphorylation of STAT3(p-STAT3)and decreased the percentage of ALDH1A1-positive CRC cells.The addition of SH-4-54 dissociated colorectal spheroids and decreased the expression of stemness markers,including ALDH1A1,CD44 and Nanog.SH-4-54 treatment decreased IL-6/JAK2/STAT3 signaling by inhibiting p-STAT3 and thus inhibited spheroid formation by SW480 and LoVo cells.Moreover,SH-4-54 treatment inhibited indicators of malignancy,including cell proliferation,invasion,and tumor formation,in CSCs in vitro and in vivo.Notably,SH-4-54 treatment significantly increased chemosensitivity to oxaplatin.CONCLUSION Taken together,these results indicate that SH-4-54 is a promising molecule that exerts antitumor effects on colorectal CSCs by inhibiting STAT3 signaling.展开更多
BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohor...BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed t...BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed that CRC patients may experience postoperative cognitive dysfunction(POCD).AIM To establish a risk prediction model for POCD in CRC patients and investigate the preventive value of dexmedetomidine(DEX).METHODS A retrospective analysis was conducted on clinical data from 140 CRC patients who underwent surgery at the People’s Hospital of Qian Nan from February 2020 to May 2024.Patients were allocated into a modeling group(n=98)and a validation group(n=42)in a 7:3 ratio.General clinical data were collected.Additionally,in the modeling group,patients who received DEX preoperatively were incorporated into the observation group(n=54),while those who did not were placed in the control group(n=44).The incidence of POCD was recorded for both cohorts.Data analysis was performed using statistical product and service solutions 20.0,with t-tests orχ2 tests employed for group comparisons based on the data type.Least absolute shrinkage and selection operator regression was applied to identify influencing factors and reduce the impact of multicollinear predictors among variables.Multivariate analysis was carried out using Logistic regression.Based on the identified risk factors,a risk prediction model for POCD in CRC patients was developed,and the predictive value of these risk factors was evaluated.RESULTS Significant differences were observed between the cognitive dysfunction group and the non-cognitive dysfunction group in diabetes status,alcohol consumption,years of education,anesthesia duration,intraoperative blood loss,intraoperative hypoxemia,use of DEX during surgery,intraoperative use of vasoactive drugs,surgical time,systemic inflammatory response syndrome(SIRS)score(P<0.05).Multivariate Logistic regression analysis identified that diabetes[odds ratio(OR)=4.679,95%confidence interval(CI)=1.382-15.833],alcohol consumption(OR=5.058,95%CI:1.255-20.380),intraoperative hypoxemia(OR=4.697,95%CI:1.380-15.991),no use of DEX during surgery(OR=3.931,95%CI:1.383-11.175),surgery duration≥90 minutes(OR=4.894,95%CI:1.377-17.394),and a SIRS score≥3(OR=4.133,95%CI:1.323-12.907)were independent risk factors for POCD in CRC patients(P<0.05).A risk prediction model for POCD was constructed using diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score as factors.A receiver operator characteristic curve analysis of these factors revealed the model’s predictive sensitivity(88.56%),specificity(70.64%),and area under the curve(AUC)(AUC=0.852,95%CI:0.773-0.919).The model was validated using 42 CRC patients who met the inclusion criteria,demonstrating sensitivity(80.77%),specificity(81.25%),and accuracy(80.95%),and AUC(0.805)in diagnosing cognitive impairment,with a 95%CI:0.635-0.896.CONCLUSION Logistic regression analysis identified that diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score vigorously influenced the occurrence of POCD.The risk prediction model based on these factors demonstrated good predictive performance for POCD in CRC individuals.This study offers valuable insights for clinical practice and contributes to the prevention and management of POCD under CRC circumstances.展开更多
Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression an...Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.展开更多
BACKGROUND Unraveling the pathogenesis of colorectal cancer(CRC)can aid in developing prevention and treatment strategies.Aurora kinase A(AURKA)is a key participant in mitotic control and interacts with its co-activat...BACKGROUND Unraveling the pathogenesis of colorectal cancer(CRC)can aid in developing prevention and treatment strategies.Aurora kinase A(AURKA)is a key participant in mitotic control and interacts with its co-activator,the targeting protein for Xklp2(TPX2)microtubule nucleation factor.AURKA is associated with poor clinical outcomes and high risks of CRC recurrence.AURKA/TPX2 co-overexpression in cancer may contribute to tumorigenesis.Despite its pivotal role in CRC development and progression,the action mechanism of AURKA remains unclear.Further research is needed to explore the complex interplay between AURKA and TPX2 and to develop effective targeted treatments for patients with CRC.AIM To compare effects of AURKA and TPX2 and their combined knockdown on CRC cells.METHODS We evaluated three CRC gene datasets about CRC(GSE32323,GSE25071,and GSE21510).Potential hub genes associated with CRC onset were identified using the Venn,search tool for the retrieval of interacting genes,and KOBAS platforms,with AURKA and TPX2 emerging as significant factors.Subsequently,cell models with knockdown of AURKA,TPX2,or both were constructed using SW480 and LOVO cells.Quantitative real-time polymerase chain reaction,western blotting,cell counting kit-8,cell cloning assays,flow cytometry,and Transwell assays were used.RESULTS Forty-three highly expressed genes and 39 poorly expressed genes overlapped in cancer tissues compared to controls from three datasets.In the protein-protein interaction network of highly expressed genes,AURKA was one of key genes.Its combined score with TPX2 was 0.999,and their co-expression score was 0.846.In CRC cells,knockdown of AURKA,TPX2,or both reduced cell viability and colony number,while blocking G0/G1 phase and enhancing cell apoptosis.Additionally,they were weakened cell proliferation and migration abilities.Furthermore,the expression levels of B-cell lymphoma-2-Associated X,caspase 3,and tumor protein P53,and E-cadherin increased with a decrease in B-cell lymphoma-2,N-cadherin,and vimentin proteins.These effects were amplified when both AURKA and TPX2 were concurrently downregulated.CONCLUSION Combined knockdown of AURKA and TPX2 was effective in suppressing the malignant phenotype in CRC.Coinhibition of gene expression is a potential developmental direction for CRC treatment.展开更多
BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer(CRC)cells.SIRT1,an NAD+-dependent deacetylase,regulates various cellular processes,and its upregulation results in ant...BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer(CRC)cells.SIRT1,an NAD+-dependent deacetylase,regulates various cellular processes,and its upregulation results in antitumor effects.This study investigated the role of SIRT1 in metabolic reprogramming and oxaliplatin resistance in CRC cells.AIM To investigate the role of SIRT1 in metabolic reprogramming and overcoming oxaliplatin resistance in CRC cells.METHODS We performed transcriptome sequencing of human CRC parental cells and oxaliplatin-resistant cells to identify differentially expressed genes.Key regulators were identified via the LINCS database.NAD+levels were measured by flow cytometry,and the effects of SIRT1 on oxaliplatin sensitivity were assessed by MTS assays,colony formation assays,and xenograft models.Glycolytic function was measured using Western blot and Seahorse assays.RESULTS Salermide,a SIRT1 inhibitor,was identified as a candidate compound that enhances oxaliplatin resistance.In oxaliplatin-resistant cells,SIRT1 was downregulated,whereasγH2AX and PARP were upregulated.PARP activation led to NAD+depletion and SIRT1 inhibition,which were reversed by PARP inhibitor treatment.The increase in SIRT1 expression overcame oxaliplatin resistance,and while SIRT1 inhibition increased glycolysis,the increase in SIRT1 inhibited glycolysis in resistant CRC cells,which was charac-terized by reduced expression of the glycolytic enzymes PKM2 and LDHA,as well as a decreased extracellular acidification rate.The PKM2 inhibitor shikonin inhibited glycolysis and reversed oxaliplatin resistance induced by SIRT1 inhibition.CONCLUSION SIRT1 expression is reduced in oxaliplatin-resistant CRC cells due to PARP activation,which in turn increases glycolysis.Restoring SIRT1 expression reverses oxaliplatin resistance in CRC cells,offering a promising therapeutic strategy to overcome drug resistance.展开更多
This editorial provides insights into the pivotal role of checkpoint kinase 1(CHEK1)as both a biomarker and therapeutic target in colorectal cancer(CRC),based on findings from a recent study by Pang et al.Using single...This editorial provides insights into the pivotal role of checkpoint kinase 1(CHEK1)as both a biomarker and therapeutic target in colorectal cancer(CRC),based on findings from a recent study by Pang et al.Using single-cell RNA sequencing and immunohistochemistry,the study demonstrates significant CHEK1 overexpression in CRC tissues and identifies nitidine chloride as a potent CHEK1 inhibitor that disrupts DNA damage repair pathways.These findings underscore the therapeutic potential of CHEK1 inhibition and highlight the need for further research to address gaps in CRC treatment.展开更多
BACKGROUND Surgery is the first choice of treatment for patients with colorectal cancer.Traditional open surgery imparts great damage to the body of the patient and can easily cause adverse stress reactions.With the c...BACKGROUND Surgery is the first choice of treatment for patients with colorectal cancer.Traditional open surgery imparts great damage to the body of the patient and can easily cause adverse stress reactions.With the continuous development of medical technology,laparoscopic minimally invasive surgery has shown great advantages for the treatment of patients with celiac disease.AIM To investigate the short-term efficacy of laparoscopic radical surgery and traditional laparotomy for the treatment of colorectal cancer,and the differences in the risk analysis of unplanned reoperation after operation.METHODS As the research subjects,this study selected 100 patients with colorectal cancer who received surgical treatment at the Yulin First Hospital from January 2018 to January 2022.Among them,50 patients who underwent laparoscopic radical resection were selected as the research group and 50 patients who underwent traditional laparotomy were selected as the control group.Data pertaining to clinical indexes,gastrointestinal hormones,nutrition indexes,the levels of inflammatory factors,quality of life,Visual Analog Scale score,and the postoperative complications of the two groups of patients before and after treatment were collected,and the therapeutic effects in the two groups were analyzed and compared.RESULTS Compared with the control group,perioperative bleeding,peristalsis recovery time,and hospital stays were significantly shorter in the research group.After surgery,the levels of gastrin(GAS)and motilin(MTL)were decreased in both groups,and the fluctuation range of GAS and MTL observed in the research group was significantly lower than that recorded in the control group.The hemoglobin(Hb)levels increased after surgery,and the level of Hb in the research group was significantly higher compared with the control group.After the operation,the expression levels of tumor necrosis factor-α,interleukin-6,and C-reactive protein and the total incidence of complications were significantly lower in the research group compared with the control group.One year after the operation,the quality of life of the two groups was greatly improved,with the quality of life in the research group being significantly better.CONCLUSION Laparoscopy was effective for colorectal surgery by reducing the occurrence of complications and inflammatory stress reaction;moreover,the quality of life of patients was significantly improved,which warrants further promotion.展开更多
BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.G...BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.Gut microbiota is unique and can be influenced by geographic factors and habits.This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.METHODS This case-control study included 59 subjects(35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr.Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital.Microbiota examination was performed using 16S rRNA sequencing.Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs(Oxford Nanopore Technologies platform).RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index(3.28 vs 2.82,P>0.05)and a lower value on the Simpson index(0.050 vs 0.060,P>0.05).Significant differences in beta diversity were observed at the genus(P=0.002)and species levels(P=0.001).Firmicutes,Proteobacteria,Bacteroidetes,and Fusobacteria were the dominant phyla.The genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found more frequently in colorectal cancer,while Faecalibacterium,Haemophilus,and Phocaeicola were more frequently found in non-colorectal cancer.The relative abundance of Fusobacterium nucleatum,Bacteroides fragilis,Enterococcus faecalis,Campylobacter hominis,and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer.Meanwhile,Faecalibacterium prausnitzii,Faecalibacterium duncaniae,and Prevotella copri were more commonly found in non-colorectal cancer.CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer.This study was reviewed and approved by the Ethics Committee of Faculty of Medicine,Universitas Indonesia(No.KET-1517/UN2.F1/ETIK/PPM.00.02/2023).展开更多
BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer worldwide.Among patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to mortality.In recent years,immunother...BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer worldwide.Among patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to mortality.In recent years,immunotherapy has swiftly risen to prominence as a vital approach for treating a range of solid tumors,including CRC.We present a unique case of a patient suffering from CRLM,with the goal of offering an insightful example and relevant references for the treatment of CRLM.CASE SUMMARY We report a patient who experienced liver metastasis after undergoing successful surgical removal of CRC,with the postoperative pathological stage identified as pT4N2aM0.The patient has been receiving a combination treatment of Western and Traditional Chinese Medicine.Regular assessments of the patient’s condition have been conducted,encompassing evaluations of serum carcinoembryonic antigen levels,carbohydrate antigen 199,and observations of the tongue complexion and its coating.The patient achieved clinical remission after anti-programmed death-1 immunotherapy when various systemic therapies failed.Since the diagnosis of CRLM,the patient has survived for more than 6 years,surpassing the expected survival time for those with advanced CRC.CONCLUSION This case illustrates the considerable promise of anti-programmed death-1 immunotherapy in managing CRLM,especially in scenarios of drug resistance and disease progression.展开更多
BACKGROUND Colorectal cancer(CRC)remains one of the most common malignancies worldwide,with a significant subset of patients exhibiting absence of carcinoembryonic-antigen(CEA)expression.The lack of effective diagnost...BACKGROUND Colorectal cancer(CRC)remains one of the most common malignancies worldwide,with a significant subset of patients exhibiting absence of carcinoembryonic-antigen(CEA)expression.The lack of effective diagnostic method for CEA-negative CRC prevents its early treatment.AIM To identify potentially valuable biomarkers for identifying CEA-negative CRC,the hematological characteristics of patients with CEA-negative CRC was investigated.METHODS In this retrospective analysis,74 patients were included who had been pathologically confirmed to have CEA-negative CRC,along with 79 individuals diagnosed with benign colorectal conditions.The utility of various biomarkers was evaluated using analysis of the receiver operating characteristic(ROC)curve.RESULTS Compared with patients with benign colorectal diseases,those with CEA-negative CRC had lower hemoglobin-to-red blood cell distribution width ratio(HRR)and lymphocyte-to-red blood cell distribution width ratio(LRR),and higher platelet-to-lymphocyte ratio(PLR)(P<0.05).Correlation analysis showed that HRR was negatively correlated with T stage(r=-0.237),LRR was negatively correlated with T stage(r=-0.265)and distant metastasis(r=-0.321),and PLR was positively correlated with T stage(r=0.251)(all P<0.05).ROC analysis indicated that HRR outperformed LRR and PLR in identifying CEA-negative CRC.Combining HRR and PLR provided the highest area under the curve(area under the curve=0.808;sensitivity=82.43%;specificity=68.35%)for distinguishing CEA-negative CRC from benign colorectal diseases.CONCLUSION HRR,LRR,and PLR alone or in combination could be used to distinguish CEA-negative CRC from benign colorectal diseases.展开更多
BACKGROUND Heart rate variability(HRV)represents efferent vagus nerve activity,which is suggested to be related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various cancers.Therefor...BACKGROUND Heart rate variability(HRV)represents efferent vagus nerve activity,which is suggested to be related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various cancers.Therefore,this study hypothesized that HRV monitoring could predict perioperative complication(PC)in colorectal cancer(CRC)patients.AIM To investigate the prognostic value of HRV in hospitalized CRC patients.METHODS The observational studies included 87 patients who underwent CRC surgical procedures under enhanced recovery after surgery programs in a first-class hospital.The HRV parameters were compared between the PC group and the non PC(NPC)group from preoperative day 1 to postoperative day(Pod)3.In addition,inflammatory biomarkers and nutritional indicators were also analyzed.RESULTS The complication rate was 14.9%.HRV was markedly abnormal after surgery,especially in the PC group.The frequency-domain parameters(including pNN50)and time-domain parameters[including high-frequency(HF)]of HRV were significantly different between the two groups postoperatively.The pNN50 was significantly greater at Pod1 in the PC group than that in the NPC group and returned to baseline at Pod2,suggesting that patients with complications exhibited autonomic nerve dysfunction in the early postoperative period.In the PC group,HFs were also enhanced from Pod1 and were significantly higher than in the NPC group;inflammatory biomarkers were significantly elevated at Pod2 and Pod3;the levels of nutritional indicators were significantly lower at Pod1 and Pod2;and the white blood cell count was slightly elevated at Pod3.CONCLUSION HRV is independently associated with postoperative complications in patients with CRC.Abnormal HRV could predicted an increased risk of postoperative complications in CRC patients.Continuous HRV could be used to monitor complications in patients with CRC during the perioperative period.展开更多
BACKGROUND Colorectal cancer(CRC)is a common malignant tumor in the digestive system,whose main treatment comprises surgical resection,radiotherapy and chemotherapy,and targeted drug therapy.At present,the radical res...BACKGROUND Colorectal cancer(CRC)is a common malignant tumor in the digestive system,whose main treatment comprises surgical resection,radiotherapy and chemotherapy,and targeted drug therapy.At present,the radical resection of CRC is the main way of achieving an early cure.AIM To investigate the logistic regression analysis of bone metastasis after CRC surgery and related influencing factors.METHODS We selected 100 patients who underwent surgery for CRC and were admitted from February 2018 to February 2024,collected the general data of bone metastasis,and collected the pathological characteristics of patients with bone metastasis.Next,we divided them into groups with and without bone metastasis(Bone metastases group,n=44;no bone metastases group,n=56),compared the clinical data of the two groups,and analyzed the risk factors of bone metastasis using logistic regression analysis.RESULTS Among the 100 patients,the mean age was 54.33±8.45 years,and most were male(54.55%).The proportion of patients with lytic bone changes was 43.18%.The most common location of combined bone metastasis was the pelvis,whereas only 5 patients had limb transfer.There was a higher incidence of lung than of pancreatic or liver metastases.Regression analysis showed that the primary location of the cancer was rectal cancer.Lymph node involvement,lung metastasis,and no postoperative chemotherapy were the risk factors for postoperative bone metastasis in patients who underwent surgery for CRC(P<0.05).CONCLUSION Rectal cancer,lymph node involvement,complicated pulmonary metastasis,and no postoperative chemotherapy treatment can help predict high risk of bone metastasis in CRC.展开更多
BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor characterized by a high mortality rate,with significant challenges persisting in the identification and management of its metastatic stage.The role of ch...BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor characterized by a high mortality rate,with significant challenges persisting in the identification and management of its metastatic stage.The role of checkpoint kinase 1(CHEK1),a cell cycle checkpoint kinase,in CRC has not been fully clarified.We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells,indicating its potential as a novel therapeutic target for CRC therapy.AIM To investigate the expression and function of CHEK1 in CRC,this study utilizes single-cell RNA sequencing and tissue microarray data.METHODS Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset,and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues.We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expre-ssion in CRC.Molecular docking experiments were performed to explore the in-teraction between CHEK1 and the potential drug nitidine chloride(NC),as well as to investigate the influence of CHEK1 on CRC cell proliferation.RESULTS We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC,with marked upregulation of its mRNA levels in CRC tissues.Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues,and the receiver operating characteristic curve demonstrated high accuracy(area under the curve=0.964)for CHEK1 as a biomarker.Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC(standard mean difference=1.81,P<0.01),with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88,respectively.Molecular docking studies indicated that NC specifically targeted CHEK1,while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation.CONCLUSION Upregulation of CHEK1 promotes CRC cell proliferation.However,the dataset's diversity is limited,requiring further investigation into its specific mechanisms.展开更多
BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the para...BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the paradoxical role of C.albicans in CRC,aiming to determine whether it promotes or suppresses tumor development,with a focus on the mechanistic basis linked to its metabolic profile.AIM To investigate the dual role of C.albicans in the development and progression of CRC through metabolite profiling and to establish a prognostic model that integrates the microbial and metabolic interactions in CRC,providing insights into potential therapeutic strategies and clinical outcomes.METHODSA prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immuneinfiltration profiling, survival analysis, Mendelian randomization, single-cell sequencing, and spatial transcriptomics.The effects of the C. albicans metabolite mixture on CRC cells were subsequently validated in vitro. Theprimary metabolite composition was characterized using liquid chromatography-mass spectrometry.RESULTSA prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, wasestablished. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysisrevealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, andGADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC celllines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expressionlevels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolitetreatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitativeanalysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolitemixture had no effect on reactive oxygen species accumulation in CRC cells but led to a reduction in mitochondrialmembrane potential, increased intracellular lipid peroxidation, and induced apoptosis. Metabolomic profilingrevealed significant alterations, with 516 metabolites upregulated and 531 downregulated.CONCLUSIONThis study introduced a novel prognostic model for CRC risk assessment. The findings suggested that the C.albicans metabolite mixture exerted an inhibitory effect on CRC initiation.展开更多
文摘BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.
文摘In this editorial,we reviewed the article by Fadlallah et al that was recently published in the World Journal of Clinical Oncology.The article provided a comprehensive and in-depth view of the management and treatment of colorectal cancer(CRC),one of the leading causes of cancer-related morbidity and mortality worldwide.The article analyzed the therapeutic modalities and their sequencing,focusing on total neoadjuvant therapy for locally advanced rectal cancer.It highlighted the role of immunotherapy in tumors with high microsatellite instability or deficient mismatch repair,addressing recent advances that have improved prognosis and therapeutic response in localized and metastatic CRC.Innovations in surgical techniques,advanced radiotherapy,and systemic agents targeting specific mutational profiles are also discussed,reflecting on how they revolutionized clinical management.Circulating tumor DNA has emerged as a promising tool for detecting minimal residual disease,prognosis,and therapeutic monitoring,solidifying its role in precision oncology.This review emphasized the importance of technological and therapeutic advancements in improving clinical outcomes and personalizing CRC treatment.
基金supported by the National Natural Science Foundation of China(82072675,82273197,82173933)Fundamental Research Funds for the Central Universities(020814380160).
文摘Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.
基金Supported by Pudong New Area Science and Technology Development Fund for Livelihood Research Special Project,No.PKJ2023-Y38.
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent malignant neoplasm characterized by subtle early manifestations.AIM To investigate the correlation among serum lipid profiles,the triglyceride-glucose(TyG)index,and the atherosclerotic index(AI)in patients with CRC.Furthermore,it explored the clinical diagnostic utility of combining serum lipids with cancer antigens in the context of CRC.METHODS A retrospective analysis encompassed 277 patients with CRC and 1034 healthy individuals.RESULTS Following propensity score matching,patients with CRC exhibited significantly reduced levels of serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol(LDL-C),as well as a diminished TyG index.Conversely,they displayed elevated AI levels compared to their healthy counterparts.Patients in advanced stages exhibited lower serum levels of TG,TC,and LDL-C compared to those in early stages.Patients with positive lymph node metastasis demonstrated reduced levels of TG,LDL-C,and the TyG index.Receiver operating characteristic analysis revealed that the combination of the TyG index,carcinoembryonic antigen,and carbohydrate antigen 19-9 yielded the highest positive prediction rate for CRC at 75.3%.CONCLUSION Preoperative serum lipid profiles exhibit a robust association with patients with CRC.The concurrent assessment of multiple serum lipids and cancer antigens effectively enhances the diagnostic accuracy for CRC.
文摘In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology.Surgical resection for peritoneal metastases from colorectal cancer(CRC)has been gradually accepted in the medical oncology community.A randomized trial(PRODIGE 7)on cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)failed to prove any benefit of oxaliplatin in the overall survival of patients with peritoneal metastases from colorectal origin.Nevertheless,isolated systemic chemotherapy for CRC stage IV has demonstrated a reduced response in peritoneal metastases than that obtained in other metastatic sites such as the liver.Another tool is required in those patients to achieve more local control of the disease.Surgical groups in peritoneal surgery continue to use HIPEC in their procedures,using other agents than oxaliplatin for peritoneal cavity infusion,such as mitomycin C.These patients present with complex surgical issues to manage,and consequently a large burden of complications has to be anticipated.Therefore,identifying patients who will benefit from CRS with or without HIPEC would be of great interest.
文摘BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC patients.Although therapy may initially yield positive results,the development of drug resistance can result in treatment failure and cancer recurrence.This resistance is often attributed to the presence of cancer stem cells(CSCs).These CSCs not only contribute to therapeutic resistance but also play crucial roles in the initiation and development of tumor metastasis.AIM To investigate the antitumor effects of SH-4-54,which are mediated by targeting CSCs relative to treatment outcomes.METHODS CSCs were enriched by culturing CRC cells in serum-free medium.Hallmarks of stemness and IL-6/JAK2/STAT3 signaling were detected by Western blotting.Indicators of CSC malignancy,including proliferation,invasion,and tumor formation,were measured.RESULTS In this study,we employed SH-4-54,which exhibits anticancer activity in solid tumors through targeting the SH2 domain of both the signal transducer and activator of transcription(STAT)3 and the STAT5,and evaluated its effects on stemness and chemoresistance in colorectal CSCs.As expected,SH-4-54 treatment inhibited the phosphorylation of STAT3(p-STAT3)and decreased the percentage of ALDH1A1-positive CRC cells.The addition of SH-4-54 dissociated colorectal spheroids and decreased the expression of stemness markers,including ALDH1A1,CD44 and Nanog.SH-4-54 treatment decreased IL-6/JAK2/STAT3 signaling by inhibiting p-STAT3 and thus inhibited spheroid formation by SW480 and LoVo cells.Moreover,SH-4-54 treatment inhibited indicators of malignancy,including cell proliferation,invasion,and tumor formation,in CSCs in vitro and in vivo.Notably,SH-4-54 treatment significantly increased chemosensitivity to oxaplatin.CONCLUSION Taken together,these results indicate that SH-4-54 is a promising molecule that exerts antitumor effects on colorectal CSCs by inhibiting STAT3 signaling.
基金Supported by National Natural Science Foundation of China,No.82174461Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0201-22Technology Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A01811.
文摘BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.
基金Supported by the Research Fund of Qiannan Medical College for Nationalities,No.Qnyz202222.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed that CRC patients may experience postoperative cognitive dysfunction(POCD).AIM To establish a risk prediction model for POCD in CRC patients and investigate the preventive value of dexmedetomidine(DEX).METHODS A retrospective analysis was conducted on clinical data from 140 CRC patients who underwent surgery at the People’s Hospital of Qian Nan from February 2020 to May 2024.Patients were allocated into a modeling group(n=98)and a validation group(n=42)in a 7:3 ratio.General clinical data were collected.Additionally,in the modeling group,patients who received DEX preoperatively were incorporated into the observation group(n=54),while those who did not were placed in the control group(n=44).The incidence of POCD was recorded for both cohorts.Data analysis was performed using statistical product and service solutions 20.0,with t-tests orχ2 tests employed for group comparisons based on the data type.Least absolute shrinkage and selection operator regression was applied to identify influencing factors and reduce the impact of multicollinear predictors among variables.Multivariate analysis was carried out using Logistic regression.Based on the identified risk factors,a risk prediction model for POCD in CRC patients was developed,and the predictive value of these risk factors was evaluated.RESULTS Significant differences were observed between the cognitive dysfunction group and the non-cognitive dysfunction group in diabetes status,alcohol consumption,years of education,anesthesia duration,intraoperative blood loss,intraoperative hypoxemia,use of DEX during surgery,intraoperative use of vasoactive drugs,surgical time,systemic inflammatory response syndrome(SIRS)score(P<0.05).Multivariate Logistic regression analysis identified that diabetes[odds ratio(OR)=4.679,95%confidence interval(CI)=1.382-15.833],alcohol consumption(OR=5.058,95%CI:1.255-20.380),intraoperative hypoxemia(OR=4.697,95%CI:1.380-15.991),no use of DEX during surgery(OR=3.931,95%CI:1.383-11.175),surgery duration≥90 minutes(OR=4.894,95%CI:1.377-17.394),and a SIRS score≥3(OR=4.133,95%CI:1.323-12.907)were independent risk factors for POCD in CRC patients(P<0.05).A risk prediction model for POCD was constructed using diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score as factors.A receiver operator characteristic curve analysis of these factors revealed the model’s predictive sensitivity(88.56%),specificity(70.64%),and area under the curve(AUC)(AUC=0.852,95%CI:0.773-0.919).The model was validated using 42 CRC patients who met the inclusion criteria,demonstrating sensitivity(80.77%),specificity(81.25%),and accuracy(80.95%),and AUC(0.805)in diagnosing cognitive impairment,with a 95%CI:0.635-0.896.CONCLUSION Logistic regression analysis identified that diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score vigorously influenced the occurrence of POCD.The risk prediction model based on these factors demonstrated good predictive performance for POCD in CRC individuals.This study offers valuable insights for clinical practice and contributes to the prevention and management of POCD under CRC circumstances.
文摘Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.
文摘BACKGROUND Unraveling the pathogenesis of colorectal cancer(CRC)can aid in developing prevention and treatment strategies.Aurora kinase A(AURKA)is a key participant in mitotic control and interacts with its co-activator,the targeting protein for Xklp2(TPX2)microtubule nucleation factor.AURKA is associated with poor clinical outcomes and high risks of CRC recurrence.AURKA/TPX2 co-overexpression in cancer may contribute to tumorigenesis.Despite its pivotal role in CRC development and progression,the action mechanism of AURKA remains unclear.Further research is needed to explore the complex interplay between AURKA and TPX2 and to develop effective targeted treatments for patients with CRC.AIM To compare effects of AURKA and TPX2 and their combined knockdown on CRC cells.METHODS We evaluated three CRC gene datasets about CRC(GSE32323,GSE25071,and GSE21510).Potential hub genes associated with CRC onset were identified using the Venn,search tool for the retrieval of interacting genes,and KOBAS platforms,with AURKA and TPX2 emerging as significant factors.Subsequently,cell models with knockdown of AURKA,TPX2,or both were constructed using SW480 and LOVO cells.Quantitative real-time polymerase chain reaction,western blotting,cell counting kit-8,cell cloning assays,flow cytometry,and Transwell assays were used.RESULTS Forty-three highly expressed genes and 39 poorly expressed genes overlapped in cancer tissues compared to controls from three datasets.In the protein-protein interaction network of highly expressed genes,AURKA was one of key genes.Its combined score with TPX2 was 0.999,and their co-expression score was 0.846.In CRC cells,knockdown of AURKA,TPX2,or both reduced cell viability and colony number,while blocking G0/G1 phase and enhancing cell apoptosis.Additionally,they were weakened cell proliferation and migration abilities.Furthermore,the expression levels of B-cell lymphoma-2-Associated X,caspase 3,and tumor protein P53,and E-cadherin increased with a decrease in B-cell lymphoma-2,N-cadherin,and vimentin proteins.These effects were amplified when both AURKA and TPX2 were concurrently downregulated.CONCLUSION Combined knockdown of AURKA and TPX2 was effective in suppressing the malignant phenotype in CRC.Coinhibition of gene expression is a potential developmental direction for CRC treatment.
基金Supported by the National Natural Science Foundation of China,No.82072756Beijing Xisike Clinical Oncology Research Foundation,No.Y-HR2019-0285.
文摘BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer(CRC)cells.SIRT1,an NAD+-dependent deacetylase,regulates various cellular processes,and its upregulation results in antitumor effects.This study investigated the role of SIRT1 in metabolic reprogramming and oxaliplatin resistance in CRC cells.AIM To investigate the role of SIRT1 in metabolic reprogramming and overcoming oxaliplatin resistance in CRC cells.METHODS We performed transcriptome sequencing of human CRC parental cells and oxaliplatin-resistant cells to identify differentially expressed genes.Key regulators were identified via the LINCS database.NAD+levels were measured by flow cytometry,and the effects of SIRT1 on oxaliplatin sensitivity were assessed by MTS assays,colony formation assays,and xenograft models.Glycolytic function was measured using Western blot and Seahorse assays.RESULTS Salermide,a SIRT1 inhibitor,was identified as a candidate compound that enhances oxaliplatin resistance.In oxaliplatin-resistant cells,SIRT1 was downregulated,whereasγH2AX and PARP were upregulated.PARP activation led to NAD+depletion and SIRT1 inhibition,which were reversed by PARP inhibitor treatment.The increase in SIRT1 expression overcame oxaliplatin resistance,and while SIRT1 inhibition increased glycolysis,the increase in SIRT1 inhibited glycolysis in resistant CRC cells,which was charac-terized by reduced expression of the glycolytic enzymes PKM2 and LDHA,as well as a decreased extracellular acidification rate.The PKM2 inhibitor shikonin inhibited glycolysis and reversed oxaliplatin resistance induced by SIRT1 inhibition.CONCLUSION SIRT1 expression is reduced in oxaliplatin-resistant CRC cells due to PARP activation,which in turn increases glycolysis.Restoring SIRT1 expression reverses oxaliplatin resistance in CRC cells,offering a promising therapeutic strategy to overcome drug resistance.
文摘This editorial provides insights into the pivotal role of checkpoint kinase 1(CHEK1)as both a biomarker and therapeutic target in colorectal cancer(CRC),based on findings from a recent study by Pang et al.Using single-cell RNA sequencing and immunohistochemistry,the study demonstrates significant CHEK1 overexpression in CRC tissues and identifies nitidine chloride as a potent CHEK1 inhibitor that disrupts DNA damage repair pathways.These findings underscore the therapeutic potential of CHEK1 inhibition and highlight the need for further research to address gaps in CRC treatment.
文摘BACKGROUND Surgery is the first choice of treatment for patients with colorectal cancer.Traditional open surgery imparts great damage to the body of the patient and can easily cause adverse stress reactions.With the continuous development of medical technology,laparoscopic minimally invasive surgery has shown great advantages for the treatment of patients with celiac disease.AIM To investigate the short-term efficacy of laparoscopic radical surgery and traditional laparotomy for the treatment of colorectal cancer,and the differences in the risk analysis of unplanned reoperation after operation.METHODS As the research subjects,this study selected 100 patients with colorectal cancer who received surgical treatment at the Yulin First Hospital from January 2018 to January 2022.Among them,50 patients who underwent laparoscopic radical resection were selected as the research group and 50 patients who underwent traditional laparotomy were selected as the control group.Data pertaining to clinical indexes,gastrointestinal hormones,nutrition indexes,the levels of inflammatory factors,quality of life,Visual Analog Scale score,and the postoperative complications of the two groups of patients before and after treatment were collected,and the therapeutic effects in the two groups were analyzed and compared.RESULTS Compared with the control group,perioperative bleeding,peristalsis recovery time,and hospital stays were significantly shorter in the research group.After surgery,the levels of gastrin(GAS)and motilin(MTL)were decreased in both groups,and the fluctuation range of GAS and MTL observed in the research group was significantly lower than that recorded in the control group.The hemoglobin(Hb)levels increased after surgery,and the level of Hb in the research group was significantly higher compared with the control group.After the operation,the expression levels of tumor necrosis factor-α,interleukin-6,and C-reactive protein and the total incidence of complications were significantly lower in the research group compared with the control group.One year after the operation,the quality of life of the two groups was greatly improved,with the quality of life in the research group being significantly better.CONCLUSION Laparoscopy was effective for colorectal surgery by reducing the occurrence of complications and inflammatory stress reaction;moreover,the quality of life of patients was significantly improved,which warrants further promotion.
文摘BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.Gut microbiota is unique and can be influenced by geographic factors and habits.This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.METHODS This case-control study included 59 subjects(35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr.Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital.Microbiota examination was performed using 16S rRNA sequencing.Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs(Oxford Nanopore Technologies platform).RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index(3.28 vs 2.82,P>0.05)and a lower value on the Simpson index(0.050 vs 0.060,P>0.05).Significant differences in beta diversity were observed at the genus(P=0.002)and species levels(P=0.001).Firmicutes,Proteobacteria,Bacteroidetes,and Fusobacteria were the dominant phyla.The genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found more frequently in colorectal cancer,while Faecalibacterium,Haemophilus,and Phocaeicola were more frequently found in non-colorectal cancer.The relative abundance of Fusobacterium nucleatum,Bacteroides fragilis,Enterococcus faecalis,Campylobacter hominis,and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer.Meanwhile,Faecalibacterium prausnitzii,Faecalibacterium duncaniae,and Prevotella copri were more commonly found in non-colorectal cancer.CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer.This study was reviewed and approved by the Ethics Committee of Faculty of Medicine,Universitas Indonesia(No.KET-1517/UN2.F1/ETIK/PPM.00.02/2023).
基金Supported by the National Key R and D Program of China,No.2022YFC3500200 and No.2022YFC3500204Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,No.ZYYCXTD-C-202208+3 种基金NATCM’s Project of Highlevel Construction of Key TCM Disciplines,No.[2023]85Qing Lan Project of Jiangsu Higher Education Institutions,No.[2023]27Jiangsu Postgraduate Practice Innovation Plan,No.SJCX22_0706General Project of Universities’Philosophy and Social Science in Jiangsu Province,No.2024SJYB0564.
文摘BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer worldwide.Among patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to mortality.In recent years,immunotherapy has swiftly risen to prominence as a vital approach for treating a range of solid tumors,including CRC.We present a unique case of a patient suffering from CRLM,with the goal of offering an insightful example and relevant references for the treatment of CRLM.CASE SUMMARY We report a patient who experienced liver metastasis after undergoing successful surgical removal of CRC,with the postoperative pathological stage identified as pT4N2aM0.The patient has been receiving a combination treatment of Western and Traditional Chinese Medicine.Regular assessments of the patient’s condition have been conducted,encompassing evaluations of serum carcinoembryonic antigen levels,carbohydrate antigen 199,and observations of the tongue complexion and its coating.The patient achieved clinical remission after anti-programmed death-1 immunotherapy when various systemic therapies failed.Since the diagnosis of CRLM,the patient has survived for more than 6 years,surpassing the expected survival time for those with advanced CRC.CONCLUSION This case illustrates the considerable promise of anti-programmed death-1 immunotherapy in managing CRLM,especially in scenarios of drug resistance and disease progression.
基金Supported by Youth Project of Guangxi International Zhuang Medicine Hospital,No.[2022]203Discipline Project of Guangxi International Zhuang Medicine Hospital,No.[2021]33Research Fund of Guangxi International Zhuang Medicine Hospital,No.RCYJ202201.
文摘BACKGROUND Colorectal cancer(CRC)remains one of the most common malignancies worldwide,with a significant subset of patients exhibiting absence of carcinoembryonic-antigen(CEA)expression.The lack of effective diagnostic method for CEA-negative CRC prevents its early treatment.AIM To identify potentially valuable biomarkers for identifying CEA-negative CRC,the hematological characteristics of patients with CEA-negative CRC was investigated.METHODS In this retrospective analysis,74 patients were included who had been pathologically confirmed to have CEA-negative CRC,along with 79 individuals diagnosed with benign colorectal conditions.The utility of various biomarkers was evaluated using analysis of the receiver operating characteristic(ROC)curve.RESULTS Compared with patients with benign colorectal diseases,those with CEA-negative CRC had lower hemoglobin-to-red blood cell distribution width ratio(HRR)and lymphocyte-to-red blood cell distribution width ratio(LRR),and higher platelet-to-lymphocyte ratio(PLR)(P<0.05).Correlation analysis showed that HRR was negatively correlated with T stage(r=-0.237),LRR was negatively correlated with T stage(r=-0.265)and distant metastasis(r=-0.321),and PLR was positively correlated with T stage(r=0.251)(all P<0.05).ROC analysis indicated that HRR outperformed LRR and PLR in identifying CEA-negative CRC.Combining HRR and PLR provided the highest area under the curve(area under the curve=0.808;sensitivity=82.43%;specificity=68.35%)for distinguishing CEA-negative CRC from benign colorectal diseases.CONCLUSION HRR,LRR,and PLR alone or in combination could be used to distinguish CEA-negative CRC from benign colorectal diseases.
基金Supported by The Natural Science Foundation of Nanjing University of Chinese Medicine,No.XZR2021019The Outstanding Young Doctor Program of Jiangsu Province of Chinese Medicine,No.2023QB0140+1 种基金Project of National Clinical Research Base of Traditional Chinese Medicine in Jiangsu Province,No.JD2022SZ18The Natural Science Foundation of Nanjing University of Chinese Medicine,No.KYCX21_1710.
文摘BACKGROUND Heart rate variability(HRV)represents efferent vagus nerve activity,which is suggested to be related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various cancers.Therefore,this study hypothesized that HRV monitoring could predict perioperative complication(PC)in colorectal cancer(CRC)patients.AIM To investigate the prognostic value of HRV in hospitalized CRC patients.METHODS The observational studies included 87 patients who underwent CRC surgical procedures under enhanced recovery after surgery programs in a first-class hospital.The HRV parameters were compared between the PC group and the non PC(NPC)group from preoperative day 1 to postoperative day(Pod)3.In addition,inflammatory biomarkers and nutritional indicators were also analyzed.RESULTS The complication rate was 14.9%.HRV was markedly abnormal after surgery,especially in the PC group.The frequency-domain parameters(including pNN50)and time-domain parameters[including high-frequency(HF)]of HRV were significantly different between the two groups postoperatively.The pNN50 was significantly greater at Pod1 in the PC group than that in the NPC group and returned to baseline at Pod2,suggesting that patients with complications exhibited autonomic nerve dysfunction in the early postoperative period.In the PC group,HFs were also enhanced from Pod1 and were significantly higher than in the NPC group;inflammatory biomarkers were significantly elevated at Pod2 and Pod3;the levels of nutritional indicators were significantly lower at Pod1 and Pod2;and the white blood cell count was slightly elevated at Pod3.CONCLUSION HRV is independently associated with postoperative complications in patients with CRC.Abnormal HRV could predicted an increased risk of postoperative complications in CRC patients.Continuous HRV could be used to monitor complications in patients with CRC during the perioperative period.
文摘BACKGROUND Colorectal cancer(CRC)is a common malignant tumor in the digestive system,whose main treatment comprises surgical resection,radiotherapy and chemotherapy,and targeted drug therapy.At present,the radical resection of CRC is the main way of achieving an early cure.AIM To investigate the logistic regression analysis of bone metastasis after CRC surgery and related influencing factors.METHODS We selected 100 patients who underwent surgery for CRC and were admitted from February 2018 to February 2024,collected the general data of bone metastasis,and collected the pathological characteristics of patients with bone metastasis.Next,we divided them into groups with and without bone metastasis(Bone metastases group,n=44;no bone metastases group,n=56),compared the clinical data of the two groups,and analyzed the risk factors of bone metastasis using logistic regression analysis.RESULTS Among the 100 patients,the mean age was 54.33±8.45 years,and most were male(54.55%).The proportion of patients with lytic bone changes was 43.18%.The most common location of combined bone metastasis was the pelvis,whereas only 5 patients had limb transfer.There was a higher incidence of lung than of pancreatic or liver metastases.Regression analysis showed that the primary location of the cancer was rectal cancer.Lymph node involvement,lung metastasis,and no postoperative chemotherapy were the risk factors for postoperative bone metastasis in patients who underwent surgery for CRC(P<0.05).CONCLUSION Rectal cancer,lymph node involvement,complicated pulmonary metastasis,and no postoperative chemotherapy treatment can help predict high risk of bone metastasis in CRC.
基金Supported by Innovation Project of Guangxi Graduate Education,No.YCBZ2023096Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z20210442+1 种基金China Undergraduate Innovation and Entrepreneurship Training Program,No.S202410598185Future Academic Star of Guangxi Medical University,No.WLXSZX24101.
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor characterized by a high mortality rate,with significant challenges persisting in the identification and management of its metastatic stage.The role of checkpoint kinase 1(CHEK1),a cell cycle checkpoint kinase,in CRC has not been fully clarified.We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells,indicating its potential as a novel therapeutic target for CRC therapy.AIM To investigate the expression and function of CHEK1 in CRC,this study utilizes single-cell RNA sequencing and tissue microarray data.METHODS Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset,and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues.We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expre-ssion in CRC.Molecular docking experiments were performed to explore the in-teraction between CHEK1 and the potential drug nitidine chloride(NC),as well as to investigate the influence of CHEK1 on CRC cell proliferation.RESULTS We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC,with marked upregulation of its mRNA levels in CRC tissues.Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues,and the receiver operating characteristic curve demonstrated high accuracy(area under the curve=0.964)for CHEK1 as a biomarker.Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC(standard mean difference=1.81,P<0.01),with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88,respectively.Molecular docking studies indicated that NC specifically targeted CHEK1,while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation.CONCLUSION Upregulation of CHEK1 promotes CRC cell proliferation.However,the dataset's diversity is limited,requiring further investigation into its specific mechanisms.
基金Supported by Gansu Province Joint Fund General Program,No.24JRRA878Gansu Provincial Science and Technology Program Project,No.24JRRA1020+2 种基金Gansu Province Key Talent Program,No.2025RCXM006Teaching Research and Reform Program for Postgraduate Education at Gansu University of Traditional Chinese Medicine(GUSTCM),No.YBXM-202406Special Fund for Mentors of“Qihuang Talents”in the First-Level Discipline of Chinese Medicine,No.ZYXKBD-202415。
文摘BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the paradoxical role of C.albicans in CRC,aiming to determine whether it promotes or suppresses tumor development,with a focus on the mechanistic basis linked to its metabolic profile.AIM To investigate the dual role of C.albicans in the development and progression of CRC through metabolite profiling and to establish a prognostic model that integrates the microbial and metabolic interactions in CRC,providing insights into potential therapeutic strategies and clinical outcomes.METHODSA prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immuneinfiltration profiling, survival analysis, Mendelian randomization, single-cell sequencing, and spatial transcriptomics.The effects of the C. albicans metabolite mixture on CRC cells were subsequently validated in vitro. Theprimary metabolite composition was characterized using liquid chromatography-mass spectrometry.RESULTSA prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, wasestablished. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysisrevealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, andGADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC celllines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expressionlevels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolitetreatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitativeanalysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolitemixture had no effect on reactive oxygen species accumulation in CRC cells but led to a reduction in mitochondrialmembrane potential, increased intracellular lipid peroxidation, and induced apoptosis. Metabolomic profilingrevealed significant alterations, with 516 metabolites upregulated and 531 downregulated.CONCLUSIONThis study introduced a novel prognostic model for CRC risk assessment. The findings suggested that the C.albicans metabolite mixture exerted an inhibitory effect on CRC initiation.
