Background:Aberrant expression of RNA-binding proteins(RBPs)has been linked to a variety of diseases,including hematological disorders,cardiovascular diseases,and multiple types of cancer.Heterogeneous nuclear ribonuc...Background:Aberrant expression of RNA-binding proteins(RBPs)has been linked to a variety of diseases,including hematological disorders,cardiovascular diseases,and multiple types of cancer.Heterogeneous nuclear ribonucleoprotein C(HNRNPC),a member belonging to the heterogeneous nuclear ribonucleoprotein(hnRNP)family,plays a pivotal role in nucleic acid metabolism.Previous studies have underscored the significance of HNRNPC in tumorigenesis;however,its specific role in malignant tumor progression remains inadequately characterized.Methods:We leveraged publicly available databases,including The Cancer Genome Atlas(TCGA),to explore the potential involvement of HNRNPC across various cancers.Additionally,we performed experimental validation studies focused on liver cancer.Results:Our analysis revealed that HNRNPC is overexpressed in a wide range of common malignancies,including liver and lung cancers,and is strongly linked to unfavorable outcomes.Furthermore,HNRNPC was observed to be closely linked to tumor immunity.Through immune checkpoint analysis and immune cell infiltration assessment,HNRNPC emerged as a potential target for modulating tumor immunotherapy.Notably,silencing of HNRNPC markedly inhibited the proliferation,metastasis,and infiltration of liver cancer cells.Conclusion:In summary,our findings highlight HNRNPC as a prognostic marker in various cancers,including liver cancer,and suggest its involvement in shaping the tumor immune microenvironment.These insights offer potential avenues for improving clinical outcomes in tumors with elevated HNRNPC expression,particularly through immunotherapeutic strategies.展开更多
Despite advances in surgery,chemotherapy,and radiotherapy,the treatment of colorectal cancer(CRC)requires more personalized approaches based on tumor biology and molecular profiling.While some relevant mutations have ...Despite advances in surgery,chemotherapy,and radiotherapy,the treatment of colorectal cancer(CRC)requires more personalized approaches based on tumor biology and molecular profiling.While some relevant mutations have been associated with differential response to immunotherapy,such as RAS and BRAF mutations limiting response to anti-epithelial growth factor receptor drugs or microsatellite instability predisposing susceptibility to immune checkpoint inhibitors,the role of inflammation in dictating tumor progression and treatment response is still under investigation.Several inflammatory biomarkers have been identified to guide patient prognosis.These include the neutrophil-lymphocyte ratio,Glasgow prognostic score(GPS)and its modified version,lymphocyte-Creactive protein ratio,and platelet-lymphocyte ratio.However,these markers are not yet included in the standard clinical management of patients with CRC,and further research is needed to evaluate their efficacy in different patient populations.A recent study by Wang et al,published in the World Journal of Gastroenterology,sheds light on the prognostic significance of pan-immune-inflammation value(PIV)in CRC,particularly concerning primary tumor location.Specifically,the authors found that a high PIV was strongly correlated with worse disease-free survival in patients with left-sided colon cancer,whereas no such association was observed in patients with right-sided colon cancer.Integrating tumor location into the prognostic assessment of CRC may improve our ability to more accurately identify high-risk patients and develop personalized treatment plans that are more likely to improve patient outcomes.展开更多
Aggressive malignant brain tumors have a poor prognosis,and early detection can significantly improve treatment effectiveness and increase patient survival rates.Various methods are available for diagnosing brain tumo...Aggressive malignant brain tumors have a poor prognosis,and early detection can significantly improve treatment effectiveness and increase patient survival rates.Various methods are available for diagnosing brain tumors,with biopsy being one of the primary options.However,a biopsy is an invasive procedure that carries a risk of brain damage,highlighting the need for safer alternatives.One promising non-invasive method is liquid biopsy,which involves extracting extracellular vesicles(EVs)from different biological fluids.Most cell types can produce and release extracellular vesicles.EVs isolated from bodily fluids,along with the molecules they carry—such as proteins,nucleic acids,and lipids—can be used to diagnose brain tumors.This approach has the potential to replace labor-intensive and expensive diagnostic methods that can adversely affect patient health.This review discusses recent advancements in the use of EVs as biomarkers for diagnosing brain tumors.展开更多
Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect ...Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.展开更多
Gastric cancer(GC), with its high incidence and mortality rates, is a highly fatal cancer that is common in East Asia particularly in China. Its recurrence and metastasis are the main causes of its poor prognosis. Cir...Gastric cancer(GC), with its high incidence and mortality rates, is a highly fatal cancer that is common in East Asia particularly in China. Its recurrence and metastasis are the main causes of its poor prognosis. Circulating tumor cells(CTCs) or other blood biomarkers that are released into the circulating blood stream by tumors are thought to play a crucial role in the recurrence and metastasis of gastric cancer. Therefore, the detection of CTCs and other blood biomarkers has an important clinical significance; in fact, they can help predict the prognosis, assess the staging, monitor the therapeutic effects and determine the drug susceptibility. Recent research has identified many blood biomarkers in GC, such as various serum proteins, autoantibodies against tumor associated antigens, and cell-free DNAs. The analysis of CTCs and circulating cell-free tumor DNA(ctDNA) in the peripheral blood of patients with gastric cancer is called as liquid biopsy. These blood biomarkers provide the disease status for individuals and have clinical meaning. In this review, we focus on the recent scientific advances regarding CTCs and other blood biomarkers, and discuss their origins and clinical meaning.展开更多
Objective: Multidetector-row computed tomography(MDCT) and serum tumor biomarkers are commonly used to evaluate the preoperative lymph node metastasis and the clinical staging of gastric cancer(GC). This study intends...Objective: Multidetector-row computed tomography(MDCT) and serum tumor biomarkers are commonly used to evaluate the preoperative lymph node metastasis and the clinical staging of gastric cancer(GC). This study intends to evaluate the clinical predictive value of MDCT and serum tumor biomarkers in lymph node metastasis of GC.Methods: The clinicopathologic data of 445 GC patients who underwent radical gastrectomy were retrospectively analyzed to evaluate the diagnostic value of MDCT and serum tumor biomarkers in lymph node metastatic staging of GC before surgery.Results: With the multinomial logistic regression analysis, the independent relative factors of lymph node metastasis of GC were identified as tumor size, depth of tumor invasion, vessel invasion, vascular embolus, and soft tissue invasion. The optimal critical value of the short diameter of lymph nodes detected by MDCT scanning for evaluation of preoperative lymph node metastasis was 6.0 mm, with 75.7% as predictive accuracy of lymph node metastasis compared to the postoperative pathological results of GC patients. In addition, the critical value of the short diameter of lymph nodes combined with serum tumor biomarkers [including carbohydrate antigen(CA)-724 and CA-199] could show an enhancement of predictive sensitivity of lymph node metastasis(up to 89.3%) before surgery.Conclusions: MDCT combined with serum tumor biomarkers should be adopted to improve preoperative sensitivity and accuracy of lymph node metastasis for GC patients.展开更多
Pancreatic neuroendocrine tumors(pNETs)are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading,clinical staging,and presence of symptoms related to hormonal secretion...Pancreatic neuroendocrine tumors(pNETs)are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading,clinical staging,and presence of symptoms related to hormonal secretion.With regard to diagnosis,remarkable advances have been made:Chromogranin A is recommended as a general marker for pNETs.But other new biomarker modalities,like circulating tumor cells,multiple transcript analysis,microRNA profile,and cytokines,should be clarified in future investigations before clinical application.Therefore,the currently available serum biomarkers are insufficient for diagnosis,but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs.Surgical resection is still the only curative therapeutic option for localized pNETs.However,a debulking operation has also been proven to be effective for controlling the disease.As for drug therapy,steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor,while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs.Great progress has been achieved in the combination of systematic therapy with local control treatments.The optimal timing of local control intervention,planning of sequential therapies,and implementation of multidisciplinary care remain pending.展开更多
BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic...BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF15 promotes cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway.Thus,TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.展开更多
To evaluate the diagnosis model of serum tumor biomarker and several clinical features diagnose and classification for lung cancer, the solid protein chip technology (C-12) was used to detect the biomarkers of SF, CEA...To evaluate the diagnosis model of serum tumor biomarker and several clinical features diagnose and classification for lung cancer, the solid protein chip technology (C-12) was used to detect the biomarkers of SF, CEA, CA242, NSE, CA125, CA19-9 and CA15-3 in serum and several clinical features of tumors and benign disease in elderly lung cancer patients were collected. Set up a discriminating analysis as a function diagnostic model in clinical elderly lung cancer diagnosis and sub-type discrimination. In combination of 2 obvious clinical indicators and 2 serum markers, it is possible to provide a diagnosis tool for lung cancer. With the help of mathematic model, it is promising to reduce the misjudgment risk based on the previous experience and therefore establish a reliable diagnosing function. This model is simple, cost-effective and easy to adapt in practice, and can also be used in screening of large population.展开更多
MicroRNA-153(miR-153),belongs toa dass of small non-coding RNA.It is a aritical regulator of gene expression at the post-transcriptional lewel which interacts with the functional mRNA at 3UTR rgion and suppresses the ...MicroRNA-153(miR-153),belongs toa dass of small non-coding RNA.It is a aritical regulator of gene expression at the post-transcriptional lewel which interacts with the functional mRNA at 3UTR rgion and suppresses the expression of the mRNA.More recently,it has become apparent that dhanges in the miR-153 axpression lead to invasion,metastasis,angiogenesis and various types of tumor progression.This review summarizes the connection between dysrgulation of miR-153 and various typas of cancer progression.miR-153 regulates various signaling pathways to inhibit the proliferation and induce apoptosis in the ancer cell and also show synergistic activity with anticancer drugs.In addition to this,the oncogenic bchavior of miR-153 and their use as a potential biomarker in cancer was also reviewed.展开更多
BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to ...BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.展开更多
GSPT2 (G1 to S phase transition protein 2) has emerged as a critical regulator of the cell cycle and has garnered increased attention for its role in tumor biology in recent years. This review explores the multifacete...GSPT2 (G1 to S phase transition protein 2) has emerged as a critical regulator of the cell cycle and has garnered increased attention for its role in tumor biology in recent years. This review explores the multifaceted functions of GSPT2, highlighting its involvement in cell cycle regulation and signaling pathways, as well as its potential as a tumor biomarker. By analyzing the latest research findings, we examine the expression patterns of GSPT2 across various tumor types and its correlation with clinical outcomes, underscoring its significance in tumor initiation and progression. Furthermore, we discuss the prospects of GSPT2 as a therapeutic target, providing new insights for future research directions.展开更多
Rectal neuroendocrine neoplasms pose significant challenges due to their varied presentations and prognoses.Traditional prognostic models,while useful,often fall short of accurately predicting clinical outcomes for th...Rectal neuroendocrine neoplasms pose significant challenges due to their varied presentations and prognoses.Traditional prognostic models,while useful,often fall short of accurately predicting clinical outcomes for these patients.This article discusses the development and implications of a novel prognostic tool,the GATIS score,which aims to enhance predictive accuracy and guide treatment strategies more effectively than current methods.Utilizing data from a large cohort and employing sophisticated statistical models,the GATIS score integrates clinical and pathological markers to provide a nuanced assessment of prognosis.We evaluate the potential of this score to transform clinical decision-making processes,its integration into current medical practices,and future directions for its develo-pment.The integration of genetic markers and other biomarkers could further refine its predictive power,highlighting the ongoing need for innovation in the management of rectal neuroendocrine neoplasms.展开更多
Colorectal cancer(CRC) is a major cause of cancer death worldwide. CRC has poor prognosis and there is a crucial need for new diagnostic and prognostic biomarkers to avoid CRC-related deaths. CRC can be considered a s...Colorectal cancer(CRC) is a major cause of cancer death worldwide. CRC has poor prognosis and there is a crucial need for new diagnostic and prognostic biomarkers to avoid CRC-related deaths. CRC can be considered a sporadic disease in most cases(75%-80%), but it has been suggested that crosstalk between gene mutations(i.e., mutations of BRAF, KRAS, and p53 as well as microsatellite instability) and epigenetic alterations(i.e., DNA methylation of Cp G island promoter regions) could play a pivotal role in cancer development. A number of studies have focused on molecular testing to guide targeted and conventional treatments for patients with CRC, sometimes with contrasting results. Some of the most useful innovations in the management of CRC include the possibility to detect the absence of KRAS, BRAF, NRAS and PIK3 CA gene mutations with the subsequent choice to administer targeted adjuvant therapy with anti-epidermal growth factor receptor antibodies. Moreover, CRC patients can benefit from tests for microsatellite instability and for the detection of loss of heterozygosity of chromosome 18 q that can be helpful in guiding therapeutic decisions as regards the administration of 5-FU. The aim of this review was to summarize the most recent evidence on the possible use of genetic or epigenetic biomarkers for diagnosis, prognosis and response to therapy in CRC patients.展开更多
Solid malignancies have to develop their own blood supply for their aggressive growth and metastasis;a process known as tumor angiogenesis.Angiogenesis is largely involved in tumor survival,progression and spread,whic...Solid malignancies have to develop their own blood supply for their aggressive growth and metastasis;a process known as tumor angiogenesis.Angiogenesis is largely involved in tumor survival,progression and spread,which are known to be significantly attributed to treatment failures.Over the past decades,efforts have been made to understand the difference between nor-mal and tumor vessels.It has been demonstrated that tumor vasculature is structurally immature with chaotic and leaky phenotypes,which provides opportunities for developing novel anticancer strategies.Targeting tumor vasculature is not only a unique therapeutic interven-tion to starve neoplastic cells,but also enhances the efficacy of conventional cancer treatments.Vascular dis-rupting agents(VDAs) have been developed to disrupt the already existing neovasculature in actively growing tumors,cause catastrophic vascular shutdown within short time,and induce secondary tumor necrosis.VDAs are cytostatic;they can only inhibit tumor growth,but not eradicate the tumor.This novel drug mechanism has urged us to develop multiparametric imaging biomark-ers to monitor early hemodynamic alterations,cellular dysfunctions and metabolic impairments before tumor dimensional changes can be detected.In this article,we review the characteristics of tumor vessels,tubulin-destabilizing mechanisms of VDAs,and in vivo effects of the VDAs that have been mostly studied in preclinical studies and clinical trials.We also compare the differ-ent tumor models adopted in the preclinical studies on VDAs.Multiparametric imaging biomarkers,mainly diffu-sion-weighted imaging and dynamic contrast-enhanced imaging from magnetic resonance imaging,are evalu-ated for their potential as morphological and functional imaging biomarkers for monitoring therapeutic effects of VDAs.展开更多
In resectable colorectal liver metastasis(CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine fo...In resectable colorectal liver metastasis(CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine for clinical decision making. For several reasons, the clinical risk score appears to no longer hold the same predictive value. Some of the reasons include the ever expanding indications for liver resection, which now increasingly tend to involve extrahepatic disease, such as lung metastases(both resectable and non-resectable) and the shift in indication from "what is taken out"(e.g., how much liver has to be resected) to "what is left behind"(that is, how much functional liver tissue the patient has after resection). The latter is amenable to modifications by using adjunct techniques of portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy techniques to expand indications for liver resection. Added to this complexity is the increasing number of molecular markers, which appear to hold important prognostic and predictive information, for which some will be discussed here. Beyond characteristics of tissue-based genomic profiles will be liquid biopsies derived from circulating tumor cells and cell-free circulating tumor DNA in the blood. These markers are present in the peripheral circulation in the majority of patients with metastatic cancer disease. Circulating biomarkers may represent more readily available methods to monitor, characterize and predict cancer biology with future implications for cancer care.展开更多
Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, progn...Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs(miR NAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through m RNA targeting and, thus, are involved in many biological processes encompassing apoptosis,cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. Mi RNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miR NAs in BC that are detected with the use of highthroughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miR NAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and,at the same time, accumulating evidence has underscored the possible contribution of miR NAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via mi RNA delivery and mi RNA inhibition. The purpose of this review is to explore the ontological role of miR NAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.展开更多
Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of...Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.展开更多
BACKGROUND Colorectal cancer(CRC)imposes a tremendous burden on human health,with high morbidity and mortality.Circular ribonucleic acids(circRNAs),a new type of noncoding RNA,are considered to participate in cancer p...BACKGROUND Colorectal cancer(CRC)imposes a tremendous burden on human health,with high morbidity and mortality.Circular ribonucleic acids(circRNAs),a new type of noncoding RNA,are considered to participate in cancer pathogenesis as microRNA(miRNA)sponges.However,the dysregulation and biological functions of circRNAs in CRC remain to be explored.AIM To identify potential circRNA biomarkers of CRC and explore their functions in CRC carcinogenesis.METHODS CircRNAs and miRNAs differentially expressed in CRC tissues were identified by analyzing expression profiles from the Gene Expression Omnibus(GEO)database.Circ_0000375 and circ_0011536 were selected as CRC biomarker candidates.Quantitative real-time polymerase chain reaction was utilized to evaluate the expression of these 2 circRNAs in CRC tissues,serums and cell lines.Receiver operating characteristic curves were generated to assess the diagnostic performances of these 2 circRNAs.Then,functional experiments,including cell counting kit-8,wound healing and Transwell invasion assays,were performed after the overexpression of circ_0000375 and circ_0011536 in CRC cell lines.Furthermore,candidate target miRNAs of circ_0000375 and circ_0011536 were predicted via bioinformatics analysis.The expression levels of these miRNAs were explored in CRC cell lines and tissues from GEO datasets.A luciferase reporter assay was developed to examine the interactions between circRNAs and miRNAs.Based on the target miRNAs and downstream genes,functional enrichment analyses were applied to reveal the critical signaling pathways involved in CRC carcinogenesis.RESULTS Downregulated circ_0000375 and circ_0011536 expression was observed in CRC tissues in GSE126095,clinical CRC tissue and serum samples and CRC cell lines.The areas under the curve for circ_0000375 and circ_0011536 were 0.911 and 0.885 in CRC tissue and 0.976 and 0.982 in CRC serum,respectively.Moreover,the serum levels of these 2 circRNAs were higher in patients at 30 d postsurgery than in patients before surgery,suggesting that the serum expression of circ_0000375 and circ_0011536 is related to CRC tumorigenesis.Circ_0000375 and circ_0011536 overexpression inhibited the proliferation,migration and invasion of CRC cells.Furthermore,miR-1182 and miR-1246,which were overexpressed in CRC tissues in GSE41655,GSE49246 and GSE115513,were verified as target miRNAs of circ_0000375 and circ_0011536,respectively,by luciferase reporter assays.The downstream genes of miR-1182 and miR-1246 were enriched in some CRC-associated pathways,such as the Wnt signaling pathway.CONCLUSION Circ_0000375 and circ_0011536 may function as tumor suppressors in CRC progression,serving as novel biomarkers for CRC diagnosis and as promising candidates for therapeutic exploration.展开更多
Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used micr...Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase(GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state(E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition(EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients.Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage Ⅱ/Ⅲ. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis,allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.展开更多
文摘Background:Aberrant expression of RNA-binding proteins(RBPs)has been linked to a variety of diseases,including hematological disorders,cardiovascular diseases,and multiple types of cancer.Heterogeneous nuclear ribonucleoprotein C(HNRNPC),a member belonging to the heterogeneous nuclear ribonucleoprotein(hnRNP)family,plays a pivotal role in nucleic acid metabolism.Previous studies have underscored the significance of HNRNPC in tumorigenesis;however,its specific role in malignant tumor progression remains inadequately characterized.Methods:We leveraged publicly available databases,including The Cancer Genome Atlas(TCGA),to explore the potential involvement of HNRNPC across various cancers.Additionally,we performed experimental validation studies focused on liver cancer.Results:Our analysis revealed that HNRNPC is overexpressed in a wide range of common malignancies,including liver and lung cancers,and is strongly linked to unfavorable outcomes.Furthermore,HNRNPC was observed to be closely linked to tumor immunity.Through immune checkpoint analysis and immune cell infiltration assessment,HNRNPC emerged as a potential target for modulating tumor immunotherapy.Notably,silencing of HNRNPC markedly inhibited the proliferation,metastasis,and infiltration of liver cancer cells.Conclusion:In summary,our findings highlight HNRNPC as a prognostic marker in various cancers,including liver cancer,and suggest its involvement in shaping the tumor immune microenvironment.These insights offer potential avenues for improving clinical outcomes in tumors with elevated HNRNPC expression,particularly through immunotherapeutic strategies.
文摘Despite advances in surgery,chemotherapy,and radiotherapy,the treatment of colorectal cancer(CRC)requires more personalized approaches based on tumor biology and molecular profiling.While some relevant mutations have been associated with differential response to immunotherapy,such as RAS and BRAF mutations limiting response to anti-epithelial growth factor receptor drugs or microsatellite instability predisposing susceptibility to immune checkpoint inhibitors,the role of inflammation in dictating tumor progression and treatment response is still under investigation.Several inflammatory biomarkers have been identified to guide patient prognosis.These include the neutrophil-lymphocyte ratio,Glasgow prognostic score(GPS)and its modified version,lymphocyte-Creactive protein ratio,and platelet-lymphocyte ratio.However,these markers are not yet included in the standard clinical management of patients with CRC,and further research is needed to evaluate their efficacy in different patient populations.A recent study by Wang et al,published in the World Journal of Gastroenterology,sheds light on the prognostic significance of pan-immune-inflammation value(PIV)in CRC,particularly concerning primary tumor location.Specifically,the authors found that a high PIV was strongly correlated with worse disease-free survival in patients with left-sided colon cancer,whereas no such association was observed in patients with right-sided colon cancer.Integrating tumor location into the prognostic assessment of CRC may improve our ability to more accurately identify high-risk patients and develop personalized treatment plans that are more likely to improve patient outcomes.
基金supported by the Kazan Federal University Strategic Academic Leadership Program(PRIORITY-2030).
文摘Aggressive malignant brain tumors have a poor prognosis,and early detection can significantly improve treatment effectiveness and increase patient survival rates.Various methods are available for diagnosing brain tumors,with biopsy being one of the primary options.However,a biopsy is an invasive procedure that carries a risk of brain damage,highlighting the need for safer alternatives.One promising non-invasive method is liquid biopsy,which involves extracting extracellular vesicles(EVs)from different biological fluids.Most cell types can produce and release extracellular vesicles.EVs isolated from bodily fluids,along with the molecules they carry—such as proteins,nucleic acids,and lipids—can be used to diagnose brain tumors.This approach has the potential to replace labor-intensive and expensive diagnostic methods that can adversely affect patient health.This review discusses recent advancements in the use of EVs as biomarkers for diagnosing brain tumors.
基金supported by the grants from Shanghai Shuguang Plan Project,No.18SG15(to SC)Shanghai Outstanding Young Scholars Project+2 种基金Shanghai Talent Development Project,No.2019044(to SC)Medical-engineering cross fund of Shanghai Jiao Tong University,No.YG2022QN009(to QZ)the National Natural Science Foundation of China,No.82201558(to QZ)。
文摘Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.
基金Supported by the Guangdong Provincial Natural Science Foundation,No.2016A030313843
文摘Gastric cancer(GC), with its high incidence and mortality rates, is a highly fatal cancer that is common in East Asia particularly in China. Its recurrence and metastasis are the main causes of its poor prognosis. Circulating tumor cells(CTCs) or other blood biomarkers that are released into the circulating blood stream by tumors are thought to play a crucial role in the recurrence and metastasis of gastric cancer. Therefore, the detection of CTCs and other blood biomarkers has an important clinical significance; in fact, they can help predict the prognosis, assess the staging, monitor the therapeutic effects and determine the drug susceptibility. Recent research has identified many blood biomarkers in GC, such as various serum proteins, autoantibodies against tumor associated antigens, and cell-free DNAs. The analysis of CTCs and circulating cell-free tumor DNA(ctDNA) in the peripheral blood of patients with gastric cancer is called as liquid biopsy. These blood biomarkers provide the disease status for individuals and have clinical meaning. In this review, we focus on the recent scientific advances regarding CTCs and other blood biomarkers, and discuss their origins and clinical meaning.
基金supported in part by grants from the Programs of National Natural Science Foundation of China (No. 81572372)National Key Research and Development Program “major chronic non-infectious disease research” (No. 2016YFC1303202)National Key Research and Development Program “precision medicine research” (No. 2017YFC0908304)
文摘Objective: Multidetector-row computed tomography(MDCT) and serum tumor biomarkers are commonly used to evaluate the preoperative lymph node metastasis and the clinical staging of gastric cancer(GC). This study intends to evaluate the clinical predictive value of MDCT and serum tumor biomarkers in lymph node metastasis of GC.Methods: The clinicopathologic data of 445 GC patients who underwent radical gastrectomy were retrospectively analyzed to evaluate the diagnostic value of MDCT and serum tumor biomarkers in lymph node metastatic staging of GC before surgery.Results: With the multinomial logistic regression analysis, the independent relative factors of lymph node metastasis of GC were identified as tumor size, depth of tumor invasion, vessel invasion, vascular embolus, and soft tissue invasion. The optimal critical value of the short diameter of lymph nodes detected by MDCT scanning for evaluation of preoperative lymph node metastasis was 6.0 mm, with 75.7% as predictive accuracy of lymph node metastasis compared to the postoperative pathological results of GC patients. In addition, the critical value of the short diameter of lymph nodes combined with serum tumor biomarkers [including carbohydrate antigen(CA)-724 and CA-199] could show an enhancement of predictive sensitivity of lymph node metastasis(up to 89.3%) before surgery.Conclusions: MDCT combined with serum tumor biomarkers should be adopted to improve preoperative sensitivity and accuracy of lymph node metastasis for GC patients.
基金Supported by Guangzhou Health and Family Planning Technology Project,No.20191A011096the National Natural Science Foundation of China,No.81602172+1 种基金Guangdong Provincial Science and Technology Plan Projects,No.2016A030313769Guangzhou Science and Technology Plan of Scientific Research Projects,No.201707010323.
文摘Pancreatic neuroendocrine tumors(pNETs)are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading,clinical staging,and presence of symptoms related to hormonal secretion.With regard to diagnosis,remarkable advances have been made:Chromogranin A is recommended as a general marker for pNETs.But other new biomarker modalities,like circulating tumor cells,multiple transcript analysis,microRNA profile,and cytokines,should be clarified in future investigations before clinical application.Therefore,the currently available serum biomarkers are insufficient for diagnosis,but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs.Surgical resection is still the only curative therapeutic option for localized pNETs.However,a debulking operation has also been proven to be effective for controlling the disease.As for drug therapy,steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor,while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs.Great progress has been achieved in the combination of systematic therapy with local control treatments.The optimal timing of local control intervention,planning of sequential therapies,and implementation of multidisciplinary care remain pending.
基金Supported by National Natural Science Foundation of China,No.81870453.
文摘BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF15 promotes cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway.Thus,TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.
文摘To evaluate the diagnosis model of serum tumor biomarker and several clinical features diagnose and classification for lung cancer, the solid protein chip technology (C-12) was used to detect the biomarkers of SF, CEA, CA242, NSE, CA125, CA19-9 and CA15-3 in serum and several clinical features of tumors and benign disease in elderly lung cancer patients were collected. Set up a discriminating analysis as a function diagnostic model in clinical elderly lung cancer diagnosis and sub-type discrimination. In combination of 2 obvious clinical indicators and 2 serum markers, it is possible to provide a diagnosis tool for lung cancer. With the help of mathematic model, it is promising to reduce the misjudgment risk based on the previous experience and therefore establish a reliable diagnosing function. This model is simple, cost-effective and easy to adapt in practice, and can also be used in screening of large population.
文摘MicroRNA-153(miR-153),belongs toa dass of small non-coding RNA.It is a aritical regulator of gene expression at the post-transcriptional lewel which interacts with the functional mRNA at 3UTR rgion and suppresses the expression of the mRNA.More recently,it has become apparent that dhanges in the miR-153 axpression lead to invasion,metastasis,angiogenesis and various types of tumor progression.This review summarizes the connection between dysrgulation of miR-153 and various typas of cancer progression.miR-153 regulates various signaling pathways to inhibit the proliferation and induce apoptosis in the ancer cell and also show synergistic activity with anticancer drugs.In addition to this,the oncogenic bchavior of miR-153 and their use as a potential biomarker in cancer was also reviewed.
文摘BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.
文摘GSPT2 (G1 to S phase transition protein 2) has emerged as a critical regulator of the cell cycle and has garnered increased attention for its role in tumor biology in recent years. This review explores the multifaceted functions of GSPT2, highlighting its involvement in cell cycle regulation and signaling pathways, as well as its potential as a tumor biomarker. By analyzing the latest research findings, we examine the expression patterns of GSPT2 across various tumor types and its correlation with clinical outcomes, underscoring its significance in tumor initiation and progression. Furthermore, we discuss the prospects of GSPT2 as a therapeutic target, providing new insights for future research directions.
文摘Rectal neuroendocrine neoplasms pose significant challenges due to their varied presentations and prognoses.Traditional prognostic models,while useful,often fall short of accurately predicting clinical outcomes for these patients.This article discusses the development and implications of a novel prognostic tool,the GATIS score,which aims to enhance predictive accuracy and guide treatment strategies more effectively than current methods.Utilizing data from a large cohort and employing sophisticated statistical models,the GATIS score integrates clinical and pathological markers to provide a nuanced assessment of prognosis.We evaluate the potential of this score to transform clinical decision-making processes,its integration into current medical practices,and future directions for its develo-pment.The integration of genetic markers and other biomarkers could further refine its predictive power,highlighting the ongoing need for innovation in the management of rectal neuroendocrine neoplasms.
文摘Colorectal cancer(CRC) is a major cause of cancer death worldwide. CRC has poor prognosis and there is a crucial need for new diagnostic and prognostic biomarkers to avoid CRC-related deaths. CRC can be considered a sporadic disease in most cases(75%-80%), but it has been suggested that crosstalk between gene mutations(i.e., mutations of BRAF, KRAS, and p53 as well as microsatellite instability) and epigenetic alterations(i.e., DNA methylation of Cp G island promoter regions) could play a pivotal role in cancer development. A number of studies have focused on molecular testing to guide targeted and conventional treatments for patients with CRC, sometimes with contrasting results. Some of the most useful innovations in the management of CRC include the possibility to detect the absence of KRAS, BRAF, NRAS and PIK3 CA gene mutations with the subsequent choice to administer targeted adjuvant therapy with anti-epidermal growth factor receptor antibodies. Moreover, CRC patients can benefit from tests for microsatellite instability and for the detection of loss of heterozygosity of chromosome 18 q that can be helpful in guiding therapeutic decisions as regards the administration of 5-FU. The aim of this review was to summarize the most recent evidence on the possible use of genetic or epigenetic biomarkers for diagnosis, prognosis and response to therapy in CRC patients.
基金Supported by(partially) The grants awarded by Fonds voor Wetenschappelijk Onderzoek-Vlaanderen(FWO Vlaanderen) Impulsfinanciering project(ZWAP/05/018)Geconcerteerde Onderzoeksactie of the Flemish Government,OT project(OT/06/70)+1 种基金the K.U.Leuven Molecular Small Animal Imaging Center MoSAIC (KUL EF/05/08)the center of excellence In vivo Molecular Imaging Research of K.U.Leuven and a EU project Asia-Link CfP 2006-EuropeAid/123738/C/ACT/Multi-Proposal No.128-498/111
文摘Solid malignancies have to develop their own blood supply for their aggressive growth and metastasis;a process known as tumor angiogenesis.Angiogenesis is largely involved in tumor survival,progression and spread,which are known to be significantly attributed to treatment failures.Over the past decades,efforts have been made to understand the difference between nor-mal and tumor vessels.It has been demonstrated that tumor vasculature is structurally immature with chaotic and leaky phenotypes,which provides opportunities for developing novel anticancer strategies.Targeting tumor vasculature is not only a unique therapeutic interven-tion to starve neoplastic cells,but also enhances the efficacy of conventional cancer treatments.Vascular dis-rupting agents(VDAs) have been developed to disrupt the already existing neovasculature in actively growing tumors,cause catastrophic vascular shutdown within short time,and induce secondary tumor necrosis.VDAs are cytostatic;they can only inhibit tumor growth,but not eradicate the tumor.This novel drug mechanism has urged us to develop multiparametric imaging biomark-ers to monitor early hemodynamic alterations,cellular dysfunctions and metabolic impairments before tumor dimensional changes can be detected.In this article,we review the characteristics of tumor vessels,tubulin-destabilizing mechanisms of VDAs,and in vivo effects of the VDAs that have been mostly studied in preclinical studies and clinical trials.We also compare the differ-ent tumor models adopted in the preclinical studies on VDAs.Multiparametric imaging biomarkers,mainly diffu-sion-weighted imaging and dynamic contrast-enhanced imaging from magnetic resonance imaging,are evalu-ated for their potential as morphological and functional imaging biomarkers for monitoring therapeutic effects of VDAs.
文摘In resectable colorectal liver metastasis(CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine for clinical decision making. For several reasons, the clinical risk score appears to no longer hold the same predictive value. Some of the reasons include the ever expanding indications for liver resection, which now increasingly tend to involve extrahepatic disease, such as lung metastases(both resectable and non-resectable) and the shift in indication from "what is taken out"(e.g., how much liver has to be resected) to "what is left behind"(that is, how much functional liver tissue the patient has after resection). The latter is amenable to modifications by using adjunct techniques of portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy techniques to expand indications for liver resection. Added to this complexity is the increasing number of molecular markers, which appear to hold important prognostic and predictive information, for which some will be discussed here. Beyond characteristics of tissue-based genomic profiles will be liquid biopsies derived from circulating tumor cells and cell-free circulating tumor DNA in the blood. These markers are present in the peripheral circulation in the majority of patients with metastatic cancer disease. Circulating biomarkers may represent more readily available methods to monitor, characterize and predict cancer biology with future implications for cancer care.
文摘Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs(miR NAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through m RNA targeting and, thus, are involved in many biological processes encompassing apoptosis,cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. Mi RNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miR NAs in BC that are detected with the use of highthroughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miR NAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and,at the same time, accumulating evidence has underscored the possible contribution of miR NAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via mi RNA delivery and mi RNA inhibition. The purpose of this review is to explore the ontological role of miR NAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.
文摘Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.
基金Supported by the National Key Development Plan for Precision Medicine Research,No. 2017YFC0910002
文摘BACKGROUND Colorectal cancer(CRC)imposes a tremendous burden on human health,with high morbidity and mortality.Circular ribonucleic acids(circRNAs),a new type of noncoding RNA,are considered to participate in cancer pathogenesis as microRNA(miRNA)sponges.However,the dysregulation and biological functions of circRNAs in CRC remain to be explored.AIM To identify potential circRNA biomarkers of CRC and explore their functions in CRC carcinogenesis.METHODS CircRNAs and miRNAs differentially expressed in CRC tissues were identified by analyzing expression profiles from the Gene Expression Omnibus(GEO)database.Circ_0000375 and circ_0011536 were selected as CRC biomarker candidates.Quantitative real-time polymerase chain reaction was utilized to evaluate the expression of these 2 circRNAs in CRC tissues,serums and cell lines.Receiver operating characteristic curves were generated to assess the diagnostic performances of these 2 circRNAs.Then,functional experiments,including cell counting kit-8,wound healing and Transwell invasion assays,were performed after the overexpression of circ_0000375 and circ_0011536 in CRC cell lines.Furthermore,candidate target miRNAs of circ_0000375 and circ_0011536 were predicted via bioinformatics analysis.The expression levels of these miRNAs were explored in CRC cell lines and tissues from GEO datasets.A luciferase reporter assay was developed to examine the interactions between circRNAs and miRNAs.Based on the target miRNAs and downstream genes,functional enrichment analyses were applied to reveal the critical signaling pathways involved in CRC carcinogenesis.RESULTS Downregulated circ_0000375 and circ_0011536 expression was observed in CRC tissues in GSE126095,clinical CRC tissue and serum samples and CRC cell lines.The areas under the curve for circ_0000375 and circ_0011536 were 0.911 and 0.885 in CRC tissue and 0.976 and 0.982 in CRC serum,respectively.Moreover,the serum levels of these 2 circRNAs were higher in patients at 30 d postsurgery than in patients before surgery,suggesting that the serum expression of circ_0000375 and circ_0011536 is related to CRC tumorigenesis.Circ_0000375 and circ_0011536 overexpression inhibited the proliferation,migration and invasion of CRC cells.Furthermore,miR-1182 and miR-1246,which were overexpressed in CRC tissues in GSE41655,GSE49246 and GSE115513,were verified as target miRNAs of circ_0000375 and circ_0011536,respectively,by luciferase reporter assays.The downstream genes of miR-1182 and miR-1246 were enriched in some CRC-associated pathways,such as the Wnt signaling pathway.CONCLUSION Circ_0000375 and circ_0011536 may function as tumor suppressors in CRC progression,serving as novel biomarkers for CRC diagnosis and as promising candidates for therapeutic exploration.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China (No. SS2014AA020603)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (No. ZYLX201701)+3 种基金Beijing Municipal Science and Technology Commission (No. D1311 00005313010)the National Natural Science Foundation of China (No. 31520103905)the National High Technology Research and Development Program (“863” Program) of China (No. 2015AA020108)the Zhi-Yuan chair professorship start-up grant WF220103010 from Shanghai Jiao Tong University
文摘Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase(GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state(E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition(EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients.Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage Ⅱ/Ⅲ. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis,allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.
