Abstract
Molecular characterization of individual patients’ tumor cells is becoming increasingly important in offering effective treatment for patients in clinical practice. Recent advances in the field have indicated that circulating tumor DNA (ctDNA) has huge potential to serve as a biomarker for early detection and precision treatment as well as prognosis of hepatocellular carcinoma (HCC). As ctDNA in HCC patients harbors the molecular characteristics of HCC tumor cells, ctDNA analysis in the blood may be sufficient for convenient, non-invasive and accurate detection, providing information for HCC diagnosis, treatment and prognosis. In this review, we will summarize and discuss current trends and challenges of ctDNA application in HCC.
Highlights
Liver cancer, with 782,500 new cases and 745,500 deaths occurring worldwide in 2012, is the second leading cause of global cancer death, with China alone accounting for about 50 % of the total number of cases and deaths [1]
Qualitative analysis of abnormal concentrations of circulating tumor DNA (ctDNA) or single-gene methylation alterations alone is not recommended for hepatocellular carcinoma (HCC) diagnosis base on a meta-analysis, while combining with AFP improves the diagnostic performance [58]
More patients will allow their physicians to make therapeutic decisions guided by genetic analysis of ctDNA
Summary
With 782,500 new cases and 745,500 deaths occurring worldwide in 2012, is the second leading cause of global cancer death, with China alone accounting for about 50 % of the total number of cases and deaths [1]. Potential applications of ctDNA testing in HCC patients may include: (a) early detection of cancer; (b) monitoring of tumor heterogeneity and metastasis; (c) identification of therapeutic targets; (d) real-time evaluation of treatment response and tumor relapse; and (e) real-time assessment of evolution of drug resistance (Fig. 2) These applications require detection of genetic and epigenetic alterations in ctDNA associated with different stages of HCC (e.g. hepatocellular dysplasia, early HCC, progressed HCC and metastatic HCC) and with different treatment options or stages of treatment. Hepatitis B virus (HBV) carriers undergoing surveillance and subsequently developing HCC had significantly higher levels of RASSF1A from the time of enrollment to cancer diagnosis [18] Another gene with methylation abnormality that has been detected in HCC patients is long interspersed nucleotide elements (LINE-1) [19]. It appears that the methylation approach is better suited at present for HCC screening using plasma or serum samples
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