Tan Wan Ying, Nagabhyrava Snigdha, Ang-Olson Olivia, Das Paromita, Ladel Luisa, Sailo Bethsebie, He Linda, Sharma Anup, Ahuja Nita
Department of Surgery, Yale School of Medicine, New Haven, CT 06520-8000, USA.
Department of Internal Medicine, Norwalk Hospital, Norwalk, CT 06850, USA.
Curr Issues Mol Biol. 2024 Jun 27;46(7):6533-6565. doi: 10.3390/cimb46070390.
Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enhancing its clinical translation. The momentum of cfDNA liquid biopsy technologies in recent years has propelled epigenetics to the forefront of molecular biology. We have only begun to reveal the true potential of epigenetics in both our understanding of disease and leveraging epigenetics in the diagnostic and therapeutic domains. Recent clinical applications of epigenetics-based cfDNA liquid biopsy revolve around DNA methylation in screening and early cancer detection, leading to the development of multi-cancer early detection tests and the capability to pinpoint tissues of origin. The clinical application of epigenetics in cfDNA liquid biopsy in minimal residual disease, monitoring, and surveillance are at their initial stages. A notable advancement in fragmentation patterns analysis has created a new avenue for epigenetic biomarkers. However, the widespread application of cfDNA liquid biopsy has many challenges, including biomarker sensitivity, specificity, logistics including infrastructure and personnel, data processing, handling, results interpretation, accessibility, and cost effectiveness. Exploring and translating epigenetics in cfDNA liquid biopsy technology can transform our understanding and perception of cancer prevention and management. cfDNA liquid biopsy has great potential in precision oncology to revolutionize conventional ways of early cancer detection, monitoring residual disease, treatment response, surveillance, and drug development. Adapting the implementation of liquid biopsy workflow to the local policy worldwide and developing point-of-care testing holds great potential to overcome global cancer disparity and improve cancer outcomes.
游离DNA（cfDNA）液体活检技术的进步引发了众多临床应用呈指数级增长。虽然基于cfDNA的液体活检在癌症治疗个性化方面取得了重大进展，但液体活检中表观遗传学在临床实践中的探索和转化仍处于起步阶段。这篇综述旨在全面且深入地阐述cfDNA液体活检中表观遗传学的现状及其相关挑战。它强调了表观遗传学在cfDNA液体活检技术中的潜力，希望能促进其临床转化。近年来cfDNA液体活检技术的发展势头将表观遗传学推向了分子生物学的前沿。我们才刚刚开始揭示表观遗传学在理解疾病以及在诊断和治疗领域利用表观遗传学方面的真正潜力。基于表观遗传学的cfDNA液体活检最近的临床应用围绕着DNA甲基化在癌症筛查和早期检测中的应用，推动了多癌早期检测测试的发展以及确定肿瘤原发组织的能力。表观遗传学在cfDNA液体活检用于最小残留疾病监测方面的临床应用尚处于初始阶段。片段化模式分析的一项显著进展为表观遗传学生物标志物开辟了一条新途径。然而，cfDNA液体活检的广泛应用面临许多挑战，包括生物标志物的敏感性、特异性、后勤保障（包括基础设施和人员）、数据处理、样本处理、结果解读、可及性和成本效益等。探索并将表观遗传学转化应用于cfDNA液体活检技术可以改变我们对癌症预防和管理的理解与认知。cfDNA液体活检在精准肿瘤学中具有巨大潜力，可彻底改变早期癌症检测、监测残留疾病、治疗反应、监测和药物开发的传统方式。使液体活检工作流程的实施适应全球各地的当地政策，并开发即时检测具有巨大潜力，有望克服全球癌症差异并改善癌症治疗效果。
