Open AccessUsing circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta‐analysis
Author(s) -
Zhang Ziying,
Chen Peng,
Xie Hui,
Cao Peiguo
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2799
Subject(s) - diagnostic odds ratio , confidence interval , hepatocellular carcinoma , subgroup analysis , receiver operating characteristic , meta analysis , medicine , odds ratio , likelihood ratios in diagnostic testing , area under the curve , biomarker , oncology , gastroenterology , dna methylation , methylation , biology , genetics , dna , gene , gene expression
Purpose A meta‐analysis was formulated to appraise the diagnostic accuracy of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC). Materials and Methods We enrolled all relevant studies published until September 2019. Four primary subgroups were investigated: the subgroup of quantitative or qualitative analysis of ctDNA, the subgroup of Ras association domain family 1 isoform A RASSF1A methylation in ctDNA and the subgroup of the combined alpha‐fetoprotein (AFP) and ctDNA assay. We analyzed the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) as well as the area under the curve (AUC). Results A total of 33 qualified articles with 4113 subjects were incorporated into our meta‐analysis. The combined SEN, SPE, and DOR in quantitative studies were 0.722 (95% confidence interval (95% CI): 0.686‐0.756), 0.823 (95% CI: 0.789‐0.854), 18.532 (95% CI: 8.245‐41.657), respectively, yielding an AUC of 0.880. For qualitative studies, the corresponding value was 0.568 (95% CI: 0.548‐0.587), 0.882 (95% CI: 0.867‐0.897), 10.457 (95% CI: 7.270‐15.040) and 0.787, respectively. Detection of RASSF1A methylation yielded an AUC of 0.841, with a SEN of 0.644 (95% CI: 0.608‐0.678) and a SPE of 0.875 (95% CI: 0.847‐0.900). AFP combined with ctDNA assay achieved an AUC of 0.944, with a SEN of 0.760 (95% CI: 0.728‐00.790) and a SPE of 0.920 (95% CI: 0.893‐00.942). Conclusion Circulating tumor DNA displays a promising diagnostic potential in HCC. However, it is not independently sufficient and can serve as an assistant tool combined with AFP for HCC screening and detection.