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了解 DNA 甲基化在结直肠癌中的作用:机制、检测及临床意义。

Understanding the role of DNA methylation in colorectal cancer: Mechanisms, detection, and clinical significance.

机构信息

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China.

Division of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.

出版信息

Biochim Biophys Acta Rev Cancer. 2024 May;1879(3):189096. doi: 10.1016/j.bbcan.2024.189096. Epub 2024 Mar 17.

Abstract

Colorectal cancer (CRC) is one of the deadliest malignancies worldwide, ranking third in incidence and second in mortality. Remarkably, early stage localized CRC has a 5-year survival rate of over 90%; in stark contrast, the corresponding 5-year survival rate for metastatic CRC (mCRC) is only 14%. Compounding this problem is the staggering lack of effective therapeutic strategies. Beyond genetic mutations, which have been identified as critical instigators of CRC initiation and progression, the importance of epigenetic modifications, particularly DNA methylation (DNAm), cannot be underestimated, given that DNAm can be used for diagnosis, treatment monitoring and prognostic evaluation. This review addresses the intricate mechanisms governing aberrant DNAm in CRC and its profound impact on critical oncogenic pathways. In addition, a comprehensive review of the various techniques used to detect DNAm alterations in CRC is provided, along with an exploration of the clinical utility of cancer-specific DNAm alterations.

摘要

结直肠癌(CRC)是全球最致命的恶性肿瘤之一,发病率排名第三,死亡率排名第二。值得注意的是,早期局部 CRC 的 5 年生存率超过 90%;相比之下,转移性 CRC(mCRC)的相应 5 年生存率仅为 14%。更糟糕的是,目前缺乏有效的治疗策略。除了已被确定为 CRC 发生和进展的关键启动因素的基因突变外,表观遗传修饰(尤其是 DNA 甲基化(DNAm))的重要性也不容忽视,因为 DNAm 可用于诊断、治疗监测和预后评估。本综述探讨了调控 CRC 中异常 DNAm 的复杂机制及其对关键致癌途径的深远影响。此外,还全面回顾了用于检测 CRC 中 DNAm 改变的各种技术,并探讨了癌症特异性 DNAm 改变的临床应用。

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