Diagnostic accuracy of circulating miRNAs to discriminate hepatocellular carcinoma from liver cirrhosis: a systematic review and meta-analysis

Abstract

Introduction: Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) stand as the primary causes of global mortality. Given their profound impact, the development of highly sensitive and specific circulating diagnostic markers becomes imperative to effectively identify and differentiate between cirrhosis and HCC. Accurate diagnosis is paramount in guiding appropriate therapeutic interventions. Hence, this study aimed to evaluate the potential of microRNAs (miRNAs) in discerning between HCC and LC.

Methods: This study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, with the protocol officially registered on PROSPERO under the reference number CRD42023417494. A thorough search across multiple databases like PubMed, Embase, Scopus, Wiley Online Library, and Science Direct was conducted to identify relevant studies published from January 1, 2018, to August 10, 2023. The included studies underwent methodological quality assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 (QADAS-2) tool. The synthesis of pooled sensitivity, specificity, and other relevant diagnostic parameters employed a random-effects model and was conducted using Stata 14.0. Heterogeneity was assessed using I² and Cochrane Q, with subsequent subgroup analysis and meta-regression performed to identify potential sources of observed heterogeneity. A sensitivity analysis was performed to assess the resilience of the findings. Furthermore, Deeks' funnel plot was employed to evaluate publication bias.

Results: In this meta-analysis, we included fifteen publications, encompassing 787 HCC patients and 784 LC patients. The combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) values of miRNAs in differentiating HCC from LC were 0.84 (95% CI: 0.78-0.88), 0.79 (95% CI: 0.73-0.84), 3.9 (95% CI: 3.0-5.2), 0.21 (95% CI: 0.14-0.29), 19.44 (95% CI: 11-34), and 0.88 (95% CI: 0.85-0.91), respectively. The results of the subgroup analysis revealed that upregulated miRNA levels and miRNA assessments specifically for individuals of European descent exhibited superior diagnostic performance.

Conclusion: The results of this study suggested that circulating miRNAs, especially those that are upregulated, have the potential to function as robust and promising biomarkers in the differentiation of HCC from LC.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023475954.

Keywords: HCC; diagnostic biomarkers; hepatocellular carcinoma; liver cancer; liver cirrhosis; meta-analysis; miRNAs; non-coding RNAs.