Ng Charlotte K Y, Di Costanzo Giovan Giuseppe, Terracciano Luigi M, Piscuoglio Salvatore
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
Department of Biomedicine, Hepatology Laboratory, University of Basel, Basel, Switzerland.
Front Med (Lausanne). 2018 Mar 26;5:78. doi: 10.3389/fmed.2018.00078. eCollection 2018.
Over the past decade, the advancements in massively parallel sequencing have provided a new paradigm in biomedical research to uncover the genetic basis of human diseases. Integration of 'omics information has begun transforming clinical management of cancer patients in terms of diagnostics and treatment options, giving rise to the era of precision medicine. Currently, nucleic acids for molecular profiling for patients diagnosed with hepatocellular carcinoma (HCC) are typically obtained from resected tumor materials or transplanted neoplastic liver and occasionally from biopsies. Given the intrinsic risks associated with such invasive procedures, circulating cell-free DNA (cfDNA) has been proposed as an alternative source for tumor DNA. Circulating cfDNA is a type of cell-free nucleic acid that derives from apoptotic, necrotic, as well as living eukaryotic cells. Importantly, the detection of abnormal forms of circulating cfDNA that originate from cancer cells provides a new tool for cancer detection, disease monitoring, and molecular profiling. Currently, cfDNA is beginning to be adopted into clinical practice as a non-invasive tool to monitor disease by tracking the evolution of disease-specific genetic alterations in several major cancer types. Moreover, cfDNA is demonstrating potential clinical value as a surrogate to assess the molecular makeup of tumors and to overcome the sampling biases inherent to intra-tumor genetic heterogeneity, especially in the metastatic setting. With the improvements in 'omics and molecular biology techniques, coupled with the increasing understanding in the molecular pathogenesis of cancer, it can be anticipated that the detection and analysis of cfDNA will become more specific and sensitive and thus enable cfDNA analysis to be used as a diagnostic aid in patients with early-stage disease and perhaps even in a screening setting. In this review, we provide an overview of the latest findings on the role and potential utility of cfDNA analysis in the diagnosis, management, and screening of HCC.
在过去十年中，大规模平行测序技术的进步为生物医学研究提供了一种新的模式，以揭示人类疾病的遗传基础。“组学”信息的整合已开始在癌症患者的诊断和治疗选择方面改变临床管理方式，从而开启了精准医学时代。目前，对于被诊断为肝细胞癌（HCC）的患者，用于分子谱分析的核酸通常从切除的肿瘤组织或移植的肿瘤肝脏中获取，偶尔也从活检组织中获取。鉴于此类侵入性操作存在的固有风险，循环游离DNA（cfDNA）已被提议作为肿瘤DNA的替代来源。循环cfDNA是一种游离核酸，来源于凋亡细胞、坏死细胞以及活的真核细胞。重要的是，检测源自癌细胞的循环cfDNA异常形式为癌症检测、疾病监测和分子谱分析提供了一种新工具。目前，cfDNA正开始作为一种非侵入性工具被应用于临床实践，通过追踪几种主要癌症类型中疾病特异性基因改变的演变来监测疾病。此外，cfDNA作为评估肿瘤分子组成以及克服肿瘤内遗传异质性所固有的采样偏差的替代物，正显示出潜在的临床价值，尤其是在转移情况下。随着“组学”和分子生物学技术的改进，以及对癌症分子发病机制的认识不断加深，可以预期cfDNA的检测和分析将变得更加特异和灵敏，从而使cfDNA分析能够用作早期疾病患者甚至筛查环境中的诊断辅助手段。在本综述中，我们概述了cfDNA分析在HCC诊断、管理和筛查中的作用及潜在用途的最新研究结果。
