Colorectal cancer prognosis: insights from the tumor immune microenvironment and gut microbiota.

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-2025-517
Quan Chen, Youtao Zhou, Zikai Lin, Cuiyan Yang, Hui Chen, Chuanfeng Ke
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引用次数: 0

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Despite recent advancements in screening strategies and treatments, the prognosis of CRC patients remains poor. Emerging evidences suggest that tumor immune microenvironment (TIME) and gut microbiota play a pivotal role in CRC progression and treatment. However, the clinical utility of these findings remains limited due to the absence of robust biomarkers. We sought to establish a clinically actionable tool that could guide personalized treatment decisions and ultimately improve outcomes for CRC patients.

Methods: We analyzed differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) and identified the prognostic genes for CRC by integrating the TIME- and gut microbiota-related genes from GeneCards. Using Mendelian randomization (MR), we examined the causal relationships between the prognostic genes, gut microbiota, and CRC. We then developed a risk model and independently validated its predictive performance using The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COADREAD) dataset as an external validation cohort.

Results: We established a risk model comprising the six identified genes and found that the high-risk group had a significantly higher mortality rate than the low-risk group. Additionally, the high-risk group showed increased immune cell infiltration and a diminished response to immunotherapy. The two-step MR analysis revealed that Deltaproteobacteria and Methanobrevibacter mediated the causal relationship between the prognostic genes and CRC. Further, the risk score was shown to be an independent prognostic factor for CRC survival, and the newly established nomogram demonstrated strong concordance between the predicted and observed clinical outcomes.

Conclusions: We developed a six-gene risk model and showed that gut microbes mediate the causal link between the prognostic genes and CRC. Further research on the regulation of the TIME and gut microbiota in CRC may provide valuable insights.

结直肠癌预后:来自肿瘤免疫微环境和肠道微生物群的见解。
背景:结直肠癌(CRC)是全球第三大常见癌症。尽管最近在筛查策略和治疗方面取得了进展,但CRC患者的预后仍然很差。越来越多的证据表明,肿瘤免疫微环境(TIME)和肠道微生物群在结直肠癌的进展和治疗中起着关键作用。然而,由于缺乏强有力的生物标志物,这些发现的临床应用仍然有限。我们试图建立一个临床可操作的工具,可以指导个性化的治疗决策,并最终改善结直肠癌患者的预后。方法:我们分析了来自基因表达Omnibus (GEO)的差异表达基因(DEGs),并通过整合来自GeneCards的时间和肠道微生物群相关基因来鉴定结直肠癌的预后基因。使用孟德尔随机化(MR),我们检查了预后基因、肠道微生物群和结直肠癌之间的因果关系。然后,我们开发了一个风险模型,并使用癌症基因组图谱-结肠腺癌(TCGA-COADREAD)数据集作为外部验证队列,独立验证了其预测性能。结果:我们建立了包含6个鉴定基因的风险模型,发现高危组的死亡率明显高于低危组。此外,高危组免疫细胞浸润增加,免疫治疗反应减弱。两步磁共振分析显示,三角洲变形菌和甲烷杆菌介导预后基因与结直肠癌之间的因果关系。此外,风险评分被证明是CRC生存的独立预后因素,新建立的nomogram显示了预测和观察到的临床结果之间的高度一致性。结论:我们建立了一个六基因风险模型,并表明肠道微生物介导预后基因与结直肠癌之间的因果关系。进一步研究CRC中时间和肠道菌群的调节可能会提供有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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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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