BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attract...BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.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
基金Supported by National Natural Science Foundation of China,No.81960877University Innovation Fund of Gansu Province,No.2021A-076+5 种基金Gansu Province Science and Technology Plan(Innovation Base and Talent Plan),No.21JR7RA561Natural Science Foundation of Gansu Province,No.21JR1RA267 and No.22JR5RA582Education Technology Innovation Project of Gansu Province,No.2022A-067Innovation Fund of Higher Education of Gansu Province,No.2023A-088Gansu Province Science and Technology Plan International Cooperation Field Project,No.23YFWA0005and Open Project of Key Laboratory of Dunhuang Medicine and Transformation of Ministry of Education,No.DHYX21-07,No.DHYX22-05,and No.DHYX21-01.
文摘BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.
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.
