Circulatory miR-221 & miR-542 expression profiles as potential molecular biomarkers in Hepatitis C Virus mediated liver cirrhosis and hepatocellular carcinoma

Abstract

Chronic hepatitis C virus (cHCV) is a leading cause for liver cirrhosis (LC) and hepatocellular carcinoma (HCC) globally. So far, there is no optimal non-invasive biomarker for diagnosing HCV associated hepatic disorders. Circulatory miRNAs have drawn great attention as potential non-invasive biomarkers in various diseases. We quantified miR-221 and miR-542 levels in the plasma of 153 Egyptian patients (38 healthy controls (HC), 36 cHCV, 39 HCV-LC and 40 HCV mediated HCC groups) using qRT-PCR. All diseased groups exhibited significant upregulation in miR-221 expression (P < 0.001) with an increasing trend towards late stages (HCV-LC+HCV-HCC) as compared to early stages (cHCV). MiR-221 could significantly discriminate HCC patients from cHCV and HCV-LC with (AUC=0.698; P = 0.002) and (AUC=0.644; P = 0.032) respectively. Furthermore, miR-221 could significantly discriminate between HCC and non-HCC groups (AUC=0.670, P<0.001). HCV-LC & cHCV groups showed significant upregulation in miR-542 with remarkable downregulation in HCC group (P = 0.004). MiR-542 exhibited diagnostic power of (AUC=0.640; P = 0.044) and (AUC= 0.644; P = 0.040) for discriminating HCV-LC from HCC and cHCV groups respectively. Both miR-221 and miR-542 were significantly upregulated in cirrhotic group (HCV-LC) (P = 0.046 and P = 0.002 respectively) as compared to non-cirrhotic group (cHCV+HC). Combining both miRNAs in a panel significantly improved diagnostic performance as follows; HC and HCC (AUC=0.714, P < 0.001); HCC and LC (AUC=0.714, P = 0.001); HC and LC (AUC=0.710, P = 0.002) and also cHCV and HCC (AUC=0.672, P = 0.006). In conclusion, both miR-221 & miR-542 could stand as a standalone biomarker for staging various HCV associated disorders. Combining them would greatly enhance their diagnostic potential.

Keywords: Biomarkers; HCC; HCV; miR-221; miR-542; qRT-PCR.