Clinical Application Value of Circulating Cell-free DNA in Hepatocellular Carcinoma.

Yuyuan Zhang,Caihong Wang,Lingfang Meng,Kun Ji,Zaoqu Liu,Xinwei Han,Zhigang Ren,Lifeng Li,Xin Li,Yang Liu,Xinju Chen,Zhen Li

doi:10.3389/fmolb.2021.736330

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and a leading cause of cancer-related deaths. Due to late diagnosis, early intrahepatic metastasis and nonresponse to systemic treatments, surgical resection and/or biopsy specimens remain the gold standard for disease staging, grading and clinical decision-making. Since only a small amount of tissue was obtained in a needle biopsy, the conventional tissue biopsy is unable to represent tumor heterogeneity in HCC. For this reason, it is imperative to find a new non-invasive and easily available diagnostic tool to detect HCC at an early stage and to monitor HCC recurrence. The past decade has witnessed considerable evolution in the development of liquid biopsy technologies with the emergence of next-generation sequencing. As a liquid biopsy approach, molecular analysis of cell-free DNA (cfDNA), characterized by noninvasiveness and real-time analysis, may accurately represent the tumor burden and comprehensively reflect genetic profile of HCC. Therefore, cfDNA may be used clinically as a predictive biomarker in early diagnosis, outcome assessment, and even molecular typing. In this review, we provide an update on the recent advances made in clinical applications of cfDNA in HCC.

Highlights

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the fourth most frequently reported cause of cancer death by 2018 (Bray et al, 2018)
CfDNA is the fragmented DNA in the blood circulation which can be detected in healthy individuals and patients with cancer, and circulating tumor DNA (ctDNA) is the fraction of circulating free DNA (cfDNA) derived from primary or metastatic tumors, with the concentration ranging from 0.01 to 90% (Jen et al, 2000)
When the proportion of cfDNA derived from tumor cells accounts for only a small part of the cfDNA in the plasma, abundant errors are expected to be present in the PCR amplification and sequencing procedures

Summary

INTRODUCTION

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the fourth most frequently reported cause of cancer death by 2018 (Bray et al, 2018). CfDNA is the fragmented DNA in the blood circulation which can be detected in healthy individuals and patients with cancer, and ctDNA is the fraction of cfDNA derived from primary or metastatic tumors, with the concentration ranging from 0.01 to 90% (Jen et al, 2000). When the proportion of cfDNA derived from tumor cells accounts for only a small part of the cfDNA in the plasma, abundant errors are expected to be present in the PCR amplification and sequencing procedures To overcome this problem, unique molecule identifiers (UMIs) have emerged for detecting single nucleotide mutations at a fraction as low as 1 in 1 million molecules (Kinde et al, 2011).

Prognosis assessment exome sequencing

Findings

AUTHOR CONTRIBUTIONS