Distinct regulation mechanism of immune-related genes in left-sided and right-sided colon cancer.

IF 1.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nucleosides, Nucleotides & Nucleic Acids Pub Date : 2025-06-23 DOI:10.1080/15257770.2025.2521554

Tianfei Yi, Qi Liao, Zhiqin Jiang

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引用次数: 0

Abstract

Colon cancer is one of the most common cancers in worldwide. Emerging evidence has demonstrated distinct patterns of immune infiltration between left colon cancer (LCC) and right colon cancer (RCC), classified according to primary tumor location. However, the underlying mechanism was still unknown. Here, we identified 111 more up-regulated genes (MURGs) including PD1 (PDCD1) and CTLA4 in RCC and 166 more down-regulated genes (MDRGs) in LCC, all participating in immune-related biological processes. Notably, CD83, CXCR4 and ISL1 emerged as reversely regulated immune-related genes (IRGs) showing opposite regulation patterns between the two cancer types. Through regulatory network analysis, we found that genetic mutations predominantly drive enhanced immune infiltration in RCC through IRG up-regulation, whereas DNA methylation-mediated IRG suppression accounts for diminished immune responses in LCC. Furthermore, prognostic models based on these IRGs with high-quality were constructed in LCC and RCC respectively. In conclusion, our results provide crucial insights into the divergent immunoregulatory mechanisms governing LCC and RCC, potentially facilitating the discovery of novel biomarkers for prognosis prediction and targeted therapy.

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免疫相关基因在左右两侧结肠癌中的不同调控机制。

结肠癌是世界上最常见的癌症之一。新出现的证据表明，根据原发肿瘤的位置，左结肠癌（LCC）和右结肠癌（RCC）之间存在不同的免疫浸润模式。然而，其潜在机制尚不清楚。我们在RCC中发现了111个上调基因（MURGs），包括PD1 （PDCD1）和CTLA4，在LCC中发现了166个下调基因（MDRGs），它们都参与了免疫相关的生物学过程。值得注意的是，CD83、CXCR4和ISL1作为反向调控的免疫相关基因（IRGs）出现，在两种癌症类型中表现出相反的调控模式。通过调控网络分析，我们发现基因突变主要通过IRG上调驱动RCC免疫浸润增强，而DNA甲基化介导的IRG抑制则导致LCC免疫应答减弱。此外，在LCC和RCC中分别建立了基于这些IRGs的高质量预后模型。总之，我们的研究结果为LCC和RCC不同的免疫调节机制提供了重要的见解，可能有助于发现用于预后预测和靶向治疗的新型生物标志物。

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

Nucleosides, Nucleotides & Nucleic Acids 生物-生化与分子生物学

CiteScore

2.60

自引率

7.70%

发文量

审稿时长

6 months

期刊介绍： Nucleosides, Nucleotides & Nucleic Acids publishes research articles, short notices, and concise, critical reviews of related topics that focus on the chemistry and biology of nucleosides, nucleotides, and nucleic acids. Complete with experimental details, this all-inclusive journal emphasizes the synthesis, biological activities, new and improved synthetic methods, and significant observations related to new compounds.