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结直肠癌中DNA甲基化失调:生物标志物、免疫调节及治疗潜力

Dysregulation of DNA methylation in colorectal cancer: biomarker, immune regulation, and therapeutic potential.

作者信息

Wang Qin, Ma Chen, Yang Bin, Zheng Wenxin, Liu Xinya, Jian Gu

机构信息

School of Pharmacy, Southwest Minzu University, Chengdu, China; Department of Pathology, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

School of Pharmacy, Southwest Minzu University, Chengdu, China.

出版信息

Int Immunopharmacol. 2025 Jan 3;145:113766. doi: 10.1016/j.intimp.2024.113766. Epub 2024 Dec 6.

Abstract

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, with morbidity and mortality ranking third and second among all cancers, respectively. As a result of a sequence of genetic and DNA methylation alterations that gradually accumulate in the healthy colonic epithelium, colorectal adenomas and invasive adenocarcinomas eventually give rise to CRC. Global hypomethylation and promoter-specific DNA methylation are characteristics of CRC. The pathophysiological role of aberrant DNA methylation in malignant tumors has garnered significant interest in the last few decades. In addition, DNA methylation has been shown to play a critical role in influencing immune cell function and tumor immune evasion. This review summarizes the most recent research on DNA methylation changes in CRC, including the role of DNA methylation-related enzymes in CRC tumorigenesis and biomarkers for diagnosis, predictive and prognostic. Besides, we focus on the emerging potential of epigenetic interventions to enhance antitumor immune responses and improve the CRC clinical practice.

摘要

结直肠癌(CRC)是全球最常见的恶性肿瘤之一,其发病率和死亡率在所有癌症中分别排名第三和第二。由于一系列遗传和DNA甲基化改变在健康结肠上皮细胞中逐渐积累,大肠腺瘤和浸润性腺癌最终发展为结直肠癌。全基因组低甲基化和启动子特异性DNA甲基化是结直肠癌的特征。在过去几十年中,异常DNA甲基化在恶性肿瘤中的病理生理作用引起了人们的极大兴趣。此外,DNA甲基化已被证明在影响免疫细胞功能和肿瘤免疫逃逸中起关键作用。本综述总结了结直肠癌中DNA甲基化变化的最新研究,包括DNA甲基化相关酶在结直肠癌发生中的作用以及诊断、预测和预后生物标志物。此外,我们关注表观遗传干预在增强抗肿瘤免疫反应和改善结直肠癌临床实践方面的新潜力。

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