Background/Objectives: As one of the intensely studied epigenetic modifications, DNA methylation plays a key role in tumours, including lung cancer. Hypermethylation in tumour suppressor genes or hypomethylation in oncogenes is an important event in tumorigenesis. Minimally invasive detection of aberrant DNA methylation by liquid biopsy could provide invaluable biomarkers for lung cancer screening, early diagnosis, prognosis, and treatment, also providing a useful tool to monitor response to targeted therapies and immunotherapies. Methods: Here, we discuss the current state-of-the-art cfDNA methylation analysis of NSCLC patients, examine the unique features and limitations of detection methods in a clinical context, and highlight the last research findings in the context of main biological and immunological therapies in lung cancer. Thus, the main goal of this review is to provide a critical overview of the most important published studies that report cfDNA methylation as prognostic biomarker for resistance to target therapies and immunotherapies in lung cancer. Results and Conclusions: DNA methylation-based biomarkers show promise for lung cancer detection and management. In particular, ctDNA methylation has been shown to play an important role in detecting resistance to tyrosine kinase inhibitors and immunotherapies. Nonetheless, DNA methylation biomarkers still lack large-scale validation, actually precluding their rapid implementation in clinical practice.
背景/目的：作为备受关注的表现遗传修饰之一，DNA甲基化在包括肺癌在内的多种肿瘤中发挥关键作用。抑癌基因的高甲基化或癌基因的低甲基化是肿瘤发生过程中的重要事件。通过液体活检对异常DNA甲基化进行微创检测，可为肺癌筛查、早期诊断、预后评估及治疗提供宝贵的生物标志物，同时为监测靶向治疗和免疫治疗反应提供有效工具。方法：本文系统探讨非小细胞肺癌患者循环游离DNA甲基化分析的最新进展，剖析临床检测方法的特性与局限，并重点阐述肺癌主要生物治疗与免疫治疗领域的最新研究发现。本综述旨在对已发表的关于循环游离DNA甲基化作为肺癌靶向治疗及免疫治疗耐药预后标志物的重要研究进行批判性评述。结果与结论：基于DNA甲基化的生物标志物在肺癌检测与管理中展现出应用前景。特别是循环肿瘤DNA甲基化已被证实在酪氨酸激酶抑制剂及免疫治疗耐药监测中具有重要作用。然而，DNA甲基化标志物仍需大规模临床验证，这实际阻碍了其在临床实践中的快速应用。
肿瘤(癌症)患者之家