Optimisation of quantitative miRNA panels to consolidate the diagnostic surveillance of HBV-related hepatocellular carcinoma

PLoS One. 2018 Apr 19;13(4):e0196081. doi: 10.1371/journal.pone.0196081. eCollection 2018.


Background: Circulating microRNAs (miRNA) are biomarkers for several neoplastic diseases, including hepatocellular carcinoma (HCC). We performed a literature search, followed by experimental screening and validation in order to establish a miRNA panel in combination with the assessment of alpha-fetoprotein (AFP) levels and to evaluate its performance in HCC diagnostics.

Methods: Expression of miRNAs was quantified by quantitative PCR (qPCR) in 406 serum samples from 118 Vietnamese patients with hepatitis B (HBV)-related HCC, 69 patients with HBV-related liver cirrhosis (LC), 100 chronic hepatitis B (CHB) patients and 119 healthy controls (HC).

Results: Three miRNAs (mir-21, mir-122, mir-192) were expressed differentially among the studied subgroups and positively correlated with AFP levels. The individual miRNAs mir-21, mir-122, mir192 or the triplex miRNA panel showed high diagnostic accuracy for HCC (HCC vs. CHB, AUC = 0.906; HCC vs. CHB+LC, AUC = 0.81; HCC vs. CHB+LC+HC, AUC = 0.854). When AFP levels were ≤20ng/ml, the triplex miRNA panel still was accurate in distinguishing HCC from the other conditions (CHB, AUC = 0.922; CHB+LC, AUC = 0.836; CHB+LC+HC, AUC = 0.862). When AFP levels were used in combination with the triplex miRNA panel, the diagnostic performance was significantly improved in discriminating HCC from the other groups (LC, AUC = 0.887; CHB, AUC = 0.948; CHB+LC, AUC = 0.887).

Conclusions: The three miRNAs mir-21, mir-122, mir-192, together with AFP, are biomarkers that may be applied to improve diagnostics of HCC in HBV patients, especially in HBV-related LC patients with normal AFP levels or HCC patients with small tumor sizes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / etiology*
  • Case-Control Studies
  • Disease Susceptibility
  • Early Detection of Cancer / methods
  • Female
  • Gene Expression Profiling / methods
  • Genetic Testing
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / virology
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / etiology*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • ROC Curve
  • Serologic Tests
  • Young Adult


  • Biomarkers, Tumor
  • MicroRNAs

Grant support

This study was funded by the Vietnam National Foundation for Science and Technology Development (http://www.nafosted.gov.vn). (NAFOSTED) under grant number 106-YS.02-2016.20 The funding agency had no role in study design, data collection and analysis, decision to publish, and/or preparation of the manuscript.