Song Qiao, Shangzhen Yang, Hua Hua, Chengtao Mao, Xiaolong Li, Cai Cheng, Hongguo Guo, Wanling Lu
{"title":"通过程序性细胞死亡途径的多组学分析鉴定结直肠癌的预后生物标志物。","authors":"Song Qiao, Shangzhen Yang, Hua Hua, Chengtao Mao, Xiaolong Li, Cai Cheng, Hongguo Guo, Wanling Lu","doi":"10.21037/jgo-2024-861","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Programmed cell death (PCD) pathways, including autophagy, ferroptosis, cuproptosis, neutrophil extracellular trap formation (NETosis), and paraptosis, are central to tumor biology and hold potential as therapeutic targets in colorectal cancer (CRC). The aim of this study is to use multi-omics data to analyze the role of PCD in CRC.</p><p><strong>Methods: </strong>We conducted a multi-omics analysis using data from The Cancer Genome Atlas (TCGA), single-cell sequencing, and spatial transcriptomics to investigate the expression profiles, prognostic significance, and functional effects of PCD-associated genes in CRC. Key prognostic genes were identified through gene set variation analysis (GSVA), single-sample gene set enrichment analysis (ssGSEA), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression modeling.</p><p><strong>Results: </strong>Our analysis identified five PCD pathways with significant prognostic relevance in CRC, particularly autophagy and cuproptosis. Pan-cancer analyses highlighted unique and shared expression patterns of PCD-related genes across diverse cancer types, revealing their differential roles in cancer progression. Dynamic network biomarker (DNB) modeling pinpointed stage-specific critical transitions in PCD pathway activity, suggesting temporal variations in pathway influence on tumor progression. Functional assays demonstrated that overexpression of nuclear receptor coactivator 4 (<i>NCOA4</i>), an autophagy-related gene, suppressed CRC cell migration and invasion while promoting apoptosis, validating its anti-tumor role in CRC.</p><p><strong>Conclusions: </strong>This study underscores the prognostic significance of PCD pathways in CRC, highlighting their potential as biomarkers and therapeutic targets. By identifying core genes within these pathways and elucidating their temporal effects on tumor progression, we provide a comprehensive foundation for future research into PCD-targeted therapies in CRC, aiming to enhance personalized treatment strategies.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1503-1520"},"PeriodicalIF":2.0000,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432933/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of prognostic biomarkers in colorectal cancer through multi-omics profiling of programmed cell death pathways.\",\"authors\":\"Song Qiao, Shangzhen Yang, Hua Hua, Chengtao Mao, Xiaolong Li, Cai Cheng, Hongguo Guo, Wanling Lu\",\"doi\":\"10.21037/jgo-2024-861\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Programmed cell death (PCD) pathways, including autophagy, ferroptosis, cuproptosis, neutrophil extracellular trap formation (NETosis), and paraptosis, are central to tumor biology and hold potential as therapeutic targets in colorectal cancer (CRC). The aim of this study is to use multi-omics data to analyze the role of PCD in CRC.</p><p><strong>Methods: </strong>We conducted a multi-omics analysis using data from The Cancer Genome Atlas (TCGA), single-cell sequencing, and spatial transcriptomics to investigate the expression profiles, prognostic significance, and functional effects of PCD-associated genes in CRC. Key prognostic genes were identified through gene set variation analysis (GSVA), single-sample gene set enrichment analysis (ssGSEA), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression modeling.</p><p><strong>Results: </strong>Our analysis identified five PCD pathways with significant prognostic relevance in CRC, particularly autophagy and cuproptosis. Pan-cancer analyses highlighted unique and shared expression patterns of PCD-related genes across diverse cancer types, revealing their differential roles in cancer progression. Dynamic network biomarker (DNB) modeling pinpointed stage-specific critical transitions in PCD pathway activity, suggesting temporal variations in pathway influence on tumor progression. Functional assays demonstrated that overexpression of nuclear receptor coactivator 4 (<i>NCOA4</i>), an autophagy-related gene, suppressed CRC cell migration and invasion while promoting apoptosis, validating its anti-tumor role in CRC.</p><p><strong>Conclusions: </strong>This study underscores the prognostic significance of PCD pathways in CRC, highlighting their potential as biomarkers and therapeutic targets. By identifying core genes within these pathways and elucidating their temporal effects on tumor progression, we provide a comprehensive foundation for future research into PCD-targeted therapies in CRC, aiming to enhance personalized treatment strategies.</p>\",\"PeriodicalId\":15841,\"journal\":{\"name\":\"Journal of gastrointestinal oncology\",\"volume\":\"16 4\",\"pages\":\"1503-1520\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432933/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of gastrointestinal oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/jgo-2024-861\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of gastrointestinal oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/jgo-2024-861","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/27 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Identification of prognostic biomarkers in colorectal cancer through multi-omics profiling of programmed cell death pathways.
Background: Programmed cell death (PCD) pathways, including autophagy, ferroptosis, cuproptosis, neutrophil extracellular trap formation (NETosis), and paraptosis, are central to tumor biology and hold potential as therapeutic targets in colorectal cancer (CRC). The aim of this study is to use multi-omics data to analyze the role of PCD in CRC.
Methods: We conducted a multi-omics analysis using data from The Cancer Genome Atlas (TCGA), single-cell sequencing, and spatial transcriptomics to investigate the expression profiles, prognostic significance, and functional effects of PCD-associated genes in CRC. Key prognostic genes were identified through gene set variation analysis (GSVA), single-sample gene set enrichment analysis (ssGSEA), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression modeling.
Results: Our analysis identified five PCD pathways with significant prognostic relevance in CRC, particularly autophagy and cuproptosis. Pan-cancer analyses highlighted unique and shared expression patterns of PCD-related genes across diverse cancer types, revealing their differential roles in cancer progression. Dynamic network biomarker (DNB) modeling pinpointed stage-specific critical transitions in PCD pathway activity, suggesting temporal variations in pathway influence on tumor progression. Functional assays demonstrated that overexpression of nuclear receptor coactivator 4 (NCOA4), an autophagy-related gene, suppressed CRC cell migration and invasion while promoting apoptosis, validating its anti-tumor role in CRC.
Conclusions: This study underscores the prognostic significance of PCD pathways in CRC, highlighting their potential as biomarkers and therapeutic targets. By identifying core genes within these pathways and elucidating their temporal effects on tumor progression, we provide a comprehensive foundation for future research into PCD-targeted therapies in CRC, aiming to enhance personalized treatment strategies.
期刊介绍:
ournal of Gastrointestinal Oncology (Print ISSN 2078-6891; Online ISSN 2219-679X; J Gastrointest Oncol; JGO), the official journal of Society for Gastrointestinal Oncology (SGO), is an open-access, international peer-reviewed journal. It is published quarterly (Sep. 2010- Dec. 2013), bimonthly (Feb. 2014 -) and openly distributed worldwide.
JGO publishes manuscripts that focus on updated and practical information about diagnosis, prevention and clinical investigations of gastrointestinal cancer treatment. Specific areas of interest include, but not limited to, multimodality therapy, markers, imaging and tumor biology.