Circulating miRNAs as novel diagnostic biomarkers in hepatocellular carcinoma detection: a meta-analysis based on 24 articles

Abstract

The diagnostic value and suitability of circulating miRNAs for the detection of hepatocellular carcinoma have been inconsistent in the literature. A meta-analysis is used to systematically evaluate the diagnostic value of circulating miRNAs. Eligible studies were selected and the heterogeneity was assessed by subgroup analysis, meta-regression, and publication bias. After strictly and comprehensive screening, the source methods, internal reference and the cut-off values of the included miRNAs were first listed. Circulating miRNAs demonstrated a relatively good diagnostic value in hepatocellular carcinoma, In the subgroup analysis, diagnosis odds ratio showed a higher accuracy with multiple miRNAs than with a single miRNA as well as with serum types than plasma types. In addition, although miRNAs have many expression patterns, the high frequency expression miRNAs (miR-21, miR-199 and miR-122) might be more specific for the diagnosis of hepatocellular carcinoma.The sources of heterogeneity might be related to the number of miRNAs and the specimen types in meta-regression. Furthermore, it’s surprised that the pooled studies were first demonstrated publication bias (P < 0.05). In conclusion, multiple miRNAs in serum have a better diagnostic value, and the publication bias was stable. To validate the potential applicability of miRNAs in the diagnosis of hepatocellular carcinoma, more rigorous studies are needed to confirm these conclusions.

Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

“…[87][88][89][90] MiRNAs can act as either oncogenes or tumor suppressors 91 and are dysregulated in HCC. 88 Circulating miR-122 and miR-21 levels potentially could be used as novel diagnostic biomarkers in HCC patients 92,93 because dysregulated miR-122 and miR-21 expression is associated with liver inflammation and HCC (►Fig. 4).…”

Elastography reduces over-medical procedures in thyroid nodules: a systematic review and meta-analysis

“…Since publication bias may cause an inaccurate threshold value, which would exaggerate clinical effects and result in potentially erroneous decision. So it is important to assess the extent of the bias and the potential impact on the conclusions [13] . In the literature on publication bias, the funnel plot is always regarded as a tool to detect the bias.…”

Investigating the potential of circulating microRNAs as non-invasive biomarkers in cirrhosis and hepatocellular carcinoma

“…For example, this study's finding of decreased circulating miRNA-151a-p in cirrhotic patients with HCC (compared with cirrhosis alone) is in contrast to another study in plasma which reported increased expression of miRNA-151a-5p in viral hepatitis-related HCC. 329 Such inter-study variation has been previously reported by others as well, 339,340 and has been a major limitation to the development of miRNAs as diagnostic biomarkers.…”

“…This inter-study variation has also been previously reported by others. 339,340 Common causes are methodology differencessuch as miRNA source, quality control, RNA isolation, qRT-PCR strategy or data normalisationhighlighting the urgent need for standardised methods and reporting for cell-free miRNAs. 229,341 This study contributes to the considerable interest over recent years in miRNAs as biomarkers of chronic liver disease.…”

“…229,341 This study contributes to the considerable interest over recent years in miRNAs as biomarkers of chronic liver disease. Two recent meta-analyses 339,340 have concluded that miRNAs have great potential as non-invasive biomarkers, especially in the diagnosis of cirrhosis and HCC, and highlighted a number of candidate miRNAs. These studies found, however, that the quality of studies in this area is highly variable, significant heterogeneity exists, and results are often contradictory.…”