Diagnostic performance of circulating tumor DNA as a minimally invasive biomarker for hepatocellular carcinoma: a systematic review and meta-analysis.

Content Provider	Europe PMC
Author	Li, Jia Jie Lv, Yanqing Ji, Huifan
Editor	Chen, Gang
Copyright Year	2022
Abstract	PurposeThis study aimed to assess the diagnostic performance of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC).Materials and MethodsWe enrolled all relevant studies published up to 5 January 2022. Three primary subgroups were investigated: qualitative or quantitative ctDNA analyses, combined alpha-fetoprotein (AFP), and ctDNA assay. In addition to the three primary subgroups, we also evaluated the diagnostic value of methylated SEPTIN9 (mSEPT9), which has been studied extensively in the diagnosis of hepatocellular carcinoma. After a search based on four primary databases, we used a bivariate linear mixed model to analyze the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). We also plotted hierarchical summary receiver operating characteristics (HSROC) and utilized lambda as well as the area under the curve (AUC) to create summary receiver operating characteristic (SROC) curves to estimate the diagnostic value of ctDNA.ResultsA total of 59 qualified articles with 9,766 subjects were incorporated into our meta-analysis. The integrated SEN, SPE, and DOR in the qualitative studies were 0.50 (95% CI [0.43–0.56]), 0.90 (95% CI [0.86–0.93]), and 8.72 (95% CI [6.18–12.32]), respectively, yielding an AUC of 0.78 and lambda of 1.93 (95% CI [1.56–2.33]). For quantitative studies, the corresponding values were 0.69 (95% CI [0.63–0.74]), 0.84 (95% CI [0.77–0.89]), 11.88 (95% CI [7.78–18.12]), 0.81, and 2.32 (95% CI [1.96–2.69]), respectively. Six studies were included to evaluate the SETP9 methylation, which yielded an AUC of 0.86, a SEN of 0.80 (95% CI [0.71–0.87]), and a SPE of 0.77 (95% CI [0.68–0.85]). Likewise, ctDNA concentration yielded an AUC of 0.73, with a SEN of 0.63 (95% CI [0.56–0.70]) and a SPE of 0.86 (95% CI [0.74–0.93]). AFP combined with ctDNA assay resulted in an AUC of 0.89, with a SEN of 0.82 (95% CI [0.77–0.86]) and a SPE of 0.84 (95% CI [0.76–0.90]).ConclusionThis study shows that circulating tumor DNA, particularly mSEPT9, shows promising diagnostic potential in HCC; however, it is not enough to diagnose HCC independently, and ctDNA combined with conventional assays such as AFP can effectively improve diagnostic performance.
Journal	Peerj
Volume Number	10
PubMed Central reference number	PMC9637356
PubMed reference number	36348665
e-ISSN	21678359
DOI	10.7717/peerj.14303
Language	English
Publisher	PeerJ Inc.
Publisher Date	2022-11-03
Publisher Place	San Diego, USA
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. ©2022 Li et al.
Subject Keyword	Circulating tumor DNA Hepatocellular carcinoma DNA Methylation mSEPT9 Meta-analysis Diagnostic performance
Content Type	Text
Resource Type	Article
Subject	Neuroscience Medicine Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology