In current clinical practice, effective cancer testing and screening paradigms are limited to specific types of cancer, exhibiting varying efficiency, acceptance, and adherence. Cell-free DNA (cfDNA) methylation profiling holds promise in providing information about the presence of malignity regardless of its type and location while leveraging blood-based liquid biopsies as a method to obtain analytical samples. However, technical difficulties, costs and challenges resulting from biological variations, tumor heterogeneity, and exogenous factors persist. This method exploits the mechanisms behind cfDNA release but faces issues like fragmentation, low concentrations, and high background noise. This review explores cfDNA methylation’s origins, means of detection, and profiling for cancer diagnostics. The critical evaluation of currently available multi-cancer early detection methods (MCEDs) as well as tests targeting single genes, emphasizing their potential and limits to refine strategies for early cancer detection, are explained. The current methodology limitations, workflows, comparisons of clinically approved liquid biopsy-based methylation tests for cancer, their utilization in companion diagnostics as well as the biological limitations of the epigenetics approach are discussed, aiming to help healthcare providers as well as researchers to orient themselves in this increasingly complex and evolving field of diagnostics.
在当前临床实践中，有效的癌症检测与筛查模式仅限于特定癌症类型，其效率、接受度和依从性存在差异。游离DNA甲基化分析有望通过血液液体活检获取分析样本，提供与恶性肿瘤类型及部位无关的疾病存在信息。然而，由生物学变异、肿瘤异质性和外源因素导致的技术难题、成本问题及挑战仍然存在。该方法虽利用cfDNA释放机制，却面临片段化、低浓度及高背景噪音等问题。本文综述探讨了cfDNA甲基化的来源、检测方法及其在癌症诊断中的分析应用，重点评估了现有多癌种早期检测方法及单基因靶向检测技术，阐明其优化早期癌症检测策略的潜力与局限。文中讨论了当前方法学的局限性、工作流程、临床已批准的液体活检甲基化癌症检测技术比较、其在伴随诊断中的应用以及表观遗传学方法的生物学限制，旨在帮助医疗从业者和研究者在这个日益复杂且快速发展的诊断领域明确方向。
Current Challenges of Methylation-Based Liquid Biopsies in Cancer Diagnostics
肿瘤(癌症)患者之家