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。

IF 2 4区 医学 Q3 GASTROENTEROLOGY & HEPATOLOGY
Journal of gastrointestinal oncology Pub Date : 2025-08-30 Epub Date: 2025-08-27 DOI:10.21037/jgo-2024-861
Song Qiao, Shangzhen Yang, Hua Hua, Chengtao Mao, Xiaolong Li, Cai Cheng, Hongguo Guo, Wanling Lu
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引用次数: 0

摘要

背景:程序性细胞死亡(PCD)途径,包括自噬、铁凋亡、铜凋亡、中性粒细胞胞外陷阱形成(NETosis)和细胞旁凋亡,是肿瘤生物学的核心,并有可能成为结直肠癌(CRC)的治疗靶点。本研究的目的是利用多组学数据分析PCD在CRC中的作用。方法:利用癌症基因组图谱(TCGA)、单细胞测序和空间转录组学数据进行多组学分析,研究结直肠癌中pcd相关基因的表达谱、预后意义和功能作用。通过基因集变异分析(GSVA)、单样本基因集富集分析(ssGSEA)、单变量Cox回归和最小绝对收缩和选择算子(LASSO)回归模型鉴定关键预后基因。结果:我们的分析确定了五种与结直肠癌预后相关的PCD途径,特别是自噬和铜增生。泛癌症分析强调了不同癌症类型中pcd相关基因的独特和共享表达模式,揭示了它们在癌症进展中的差异作用。动态网络生物标志物(DNB)模型确定了PCD通路活性中特定阶段的关键转变,表明通路影响肿瘤进展的时间变化。功能分析表明,核受体共激活因子4 (NCOA4)是一种自噬相关基因,过表达可抑制结直肠癌细胞的迁移和侵袭,同时促进细胞凋亡,证实其在结直肠癌中的抗肿瘤作用。结论:本研究强调了PCD通路在结直肠癌中的预后意义,强调了它们作为生物标志物和治疗靶点的潜力。通过识别这些通路中的核心基因并阐明其对肿瘤进展的时间效应,我们为未来研究结直肠癌的pcd靶向治疗提供了全面的基础,旨在增强个性化的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
CiteScore
3.20
自引率
0.00%
发文量
171
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.
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