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

被引:21
作者
Xiong, Yu [1 ]
Xie, Cheng-Rong [1 ]
Zhang, Sheng [1 ]
Chen, Jin [1 ]
Yin, Zhen-Yu [1 ]
机构
[1] Xiamen Univ, Zhongshan Hosp, Dept Hepatobiliary Surg, Fujian Prov Key Lab Chron Liver Dis & Hepatocellu, Xiamen 361004, Fujian, Peoples R China
来源
CANCER MANAGEMENT AND RESEARCH | 2019年 / 11卷
基金
中国国家自然科学基金;
关键词
cell-free DNA; hepatocellular carcinoma; next-generation sequencing; alpha-fetoprotein; somatic mutation; GLOBAL CANCER STATISTICS; TUMOR DNA; BLOOD; BIOMARKERS; RESISTANCE; MARKER; DRIVER; LEVEL;
D O I
10.2147/CMAR.S197455
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:5745 / 5756
页数:12
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