Prognostic Value of Circulating Tumour DNA in Asian Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Background: Circulating tumour DNA (ctDNA) is a noninvasive method of detecting tumours, and its prognostic significance in hepatocellular carcinoma (HCC) patients is controversial. We conducted a systematic review of published research data to evaluate the prognostic value of ctDNA in HCC patients.

Methods: The PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases were searched to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to January 2022. We evaluated the quality and design of these studies. The hazard ratio (HR) was used to combine the survivorship curve and univariate and multivariate results of the included studies.

Results: In total, 8 articles were included, encompassing 577 HCC patients. The results of survival curve analysis showed that ctDNA was related to poor OS and DFS, and the effect sizes were HR = 2.44, 95% CI (1.42, 4.20), =0.001; HR = 2.63, 95% CI (1.96, 3.53), < 0.001. The univariate analysis results showed that ctDNA was related to poor OS (HR = 4.48, 95% CI (1.17, 13.70), =0.003). The combined results of multivariate analysis showed that ctDNA was related to a shorter risk of OS (HR = 3.74, 95% CI (1.45, 9.65), =0.006). The univariate and multivariate descriptive analysis results showed that ctDNA was related to shorter DFS, and the effect sizes were HR = 3.28, 95% CI (1.23, 11.30), =0.011; HR = 3.01, 95% CI (1.11, 10.5), < 0.001.

Conclusion: The evidence provided by this analysis suggests that ctDNA may be a prognostic biomarker and is negatively correlated with the survival of HCC patients. Mutations in the TERT and SOCS3 promoters in ctDNA are associated with poor prognosis and are expected to become good targets for liquid biopsy and to help select treatment strategies.