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Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma

Authors Xiong Y, Xie CR, Zhang S, Chen J, Yin ZY

Received 18 December 2018

Accepted for publication 24 April 2019

Published 28 June 2019 Volume 2019:11 Pages 5745—5756


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo

Yu Xiong, Cheng-Rong Xie, Sheng Zhang, Jin Chen, Zhen-Yu Yin

Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen 361004, Fujian, People’s Republic of China

Background/aims: Circulating cell-free DNA (cfDNA) contains tumor-specific alterations and could potentially serve as “liquid biopsy”. The study was to identify a novel panel of hepatocellular carcinoma (HCC)-specific mutations in plasma cfDNA and to assess its value in the diagnosis of HCC.
Materials and methods: 33 HCC tissue, 37 blood, and 37 swab specimens were collected from HCC patients and control individuals. Genomic DNA was subjected to next-generation sequencing. The selected mutations in the plasma cfDNA in the HCC versus control groups were compared, and the diagnostic performance of cfDNA mutations was evaluated.
Results: A majority of selected mutations in the HCC tissue DNA, ranging from 52% to 84%, was detected in the matched plasma cfDNA. For the selected mutations, receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.92, sensitivity of 65%, and specificity of 100% for the diagnosis of HCC regardless of alpha-fetoprotein (AFP) status. Detection of the selected mutations in cfDNA in combination with AFP exhibited better diagnosis performance, with AUC of 0.96, sensitivity of 73%, and specificity of 100% for AFP-negative patients, whereas the AUC was 0.86 with sensitivity of 53% and specificity of 100% for AFP-positive patients. Furthermore, the rates of the selected mutations were significantly greater in recurrent HCC than in non-recurrent HCC (P<0.05).
Conclusions: This study has identified a novel panel of somatic mutations, and detection of the mutations in plasma cfDNA shows good diagnostic performance. Therefore, this approach holds promise as a novel tool for diagnosing HCC.

Keywords: cell-free DNA, hepatocellular carcinoma, next-generation sequencing, alpha-fetoprotein, somatic mutation

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