Diagnostic accuracy of circulating microRNAs for hepatitis C virus-associated hepatocellular carcinoma: a systematic review and meta-analysis

Abstract

Aims The purpose of this study was to perform an assessment of circulating microRNAs (miRNAs) as promising biomarker for hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) through a meta-analysis. Methods A comprehensive literatures search extended up to March 1, 2020 in PubMed, Cochrane library, Embase, Web of Science, Scopus and Ovid databases. The collected data were analyzed by random-effects model, the pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were used to explore the diagnostic performance of circulating miRNAs. Meta-regression and subgroup analysis were further carried out to explore the heterogeneity. Results A total of 16 articles including 3606 HCV-HCC patients and 3387 HCV patients without HCC were collected. The pooled estimates indicated miRNAs could distinguish HCC patients from chronic hepatitis C (CHC) and HCV-associated liver cirrhosis (HCV-LC), with a SEN of 0.83 (95% CI, 0.79–0.87), a SPE of 0.77 (95% CI, 0.71–0.82), a DOR of 17 (95% CI, 12–28), and an AUC of 0.87 (95% CI, 0.84–0.90). The combination of miRNAs and AFP showed a better diagnostic accuracy than each alone. Subgroup analysis demonstrated that diagnostic accuracy of miRNAs was better for plasma types, up-regulated miRNAs, and miRNA clusters. There was no evidence of publication bias in Deeks’ funnel plot. Conclusions Circulating miRNAs, especially for miRNA clusters, have a relatively high diagnostic value for HCV-HCC from CHC and HCV-LC.

Circulating microRNAs as diagnostic biomarkers for melanoma: a systematic review and meta-analysis

“…Circulating microRNAs consist of a variety of microRNAs that are present in various extracellular fluids (e.g., plasma, serum, and whole blood) and which may be released passively during apoptosis or lysis or actively by the surviving tissue cells [ 17 ]. Circulating microRNAs exist stably in the circulatory system bound to proteins to avoid catabolism, and can be used as biomarkers for early diagnosis, therapeutic response, and prognosis of various human diseases [ 18 – 20 ]. In recent years, several studies have demonstrated the potential of circulating microRNAs as biomarkers in the early diagnosis of melanoma, but evidence-based data is still lacking [ 21 – 24 ].…”

Systematic integration of molecular and clinical approaches in HCV-induced hepatocellular carcinoma

“…Evidence demonstrate miRNAs as major regulators of HCV infection including HCV replication and distinguishing chronic HCV patients, and liver disease progression such as HCC [ 34 , 35 ]. MiRNAs, especially miRNA clusters, have high diagnostic value for HCV-HCC [ 36 ]. Dysregulation of miRNAs due to HCV infection occurs via multiple pathways, such as the immune response, lipid metabolism, and cell cycle pathways [ 37 ].…”

Research progress of circulating non-coding RNA in diagnosis and treatment of hepatocellular carcinoma

“…Moreover, the level of let-7 in HCC tissues caused by hepatitis C virus infection is lower than that in healthy people, and its circulating level is also negatively correlated with the degree of liver cirrhosis (47), indicating that the decreased level of let-7 family in the circulation should be related to HCV infection. Downregulation of the let-7 family leads to increased production of IL-10 by T cells, which in turn confers an important survival advantage to the virus by manipulating the host immune response (48). Subsequent studies have also found that the level of let-7i in the circulation after antiviral therapy can be used as a biomarker for the progression of HCC (32).…”