Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma
Yu Xiong, Cheng-Rong Xie, Sheng Zhang, Jin Chen, Zhen-Yu YinDepartment 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 ChinaBackground/aims:...
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doaj-e4917794caf24fc882808bb5c434fe9f2020-11-25T01:11:33ZengDove Medical PressCancer Management and Research1179-13222019-06-01Volume 115745575646661Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinomaXiong YXie CRZhang SChen JYin ZYYu Xiong, Cheng-Rong Xie, Sheng Zhang, Jin Chen, Zhen-Yu YinDepartment 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 ChinaBackground/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 mutationhttps://www.dovepress.com/detection-of-a-novel-panel-of-somatic-mutations-in-plasma-cell-free-dn-peer-reviewed-article-CMARCell-free DNAhepatocellular carcinomanext-generation sequencingalpha-fetoprotein;somatic mutation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiong Y Xie CR Zhang S Chen J Yin ZY |
spellingShingle |
Xiong Y Xie CR Zhang S Chen J Yin ZY Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma Cancer Management and Research Cell-free DNA hepatocellular carcinoma next-generation sequencing alpha-fetoprotein; somatic mutation |
author_facet |
Xiong Y Xie CR Zhang S Chen J Yin ZY |
author_sort |
Xiong Y |
title |
Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma |
title_short |
Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma |
title_full |
Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma |
title_fullStr |
Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma |
title_full_unstemmed |
Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma |
title_sort |
detection of a novel panel of somatic mutations in plasma cell-free dna and its diagnostic value in hepatocellular carcinoma |
publisher |
Dove Medical Press |
series |
Cancer Management and Research |
issn |
1179-1322 |
publishDate |
2019-06-01 |
description |
Yu Xiong, Cheng-Rong Xie, Sheng Zhang, Jin Chen, Zhen-Yu YinDepartment 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 ChinaBackground/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 |
topic |
Cell-free DNA hepatocellular carcinoma next-generation sequencing alpha-fetoprotein; somatic mutation |
url |
https://www.dovepress.com/detection-of-a-novel-panel-of-somatic-mutations-in-plasma-cell-free-dn-peer-reviewed-article-CMAR |
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