Circulating microRNA 9-3p and serum endocan as potential biomarkers for hepatitis C virus-related hepatocellular carcinoma

Background: The high mortality rate of hepatocellular carcinoma (HCC) in Egypt is due mainly to the increasing prevalence of hepatitis C virus infection (HCV) and late diagnosis of the carcinoma. MicroRNAs (miRNA), which regulate tumor proliferation and metastasis in HCC, may serve as a useful diagnostic approach for the early detection of HCC, thus decreasing its mortality. Meanwhile, endocan is a protein with angiogenic and inflammatory properties that are associated with tumor progression and poor outcomes.

Aim: To analyze the levels of miRNA 9-3p and endocan in HCV-infected HCC patients and correlate them with clinicopathological parameters.

Methods: We compared levels of endocan and circulating miRNA 9-3p from 35 HCV-related HCC patients to 33 patients with HCV-induced chronic liver disease and 32 age and gender matched healthy controls recruited from inpatient and outpatient clinics of the National Liver Institute, Menoufia University, Egypt in the period from January to March 2021 in a case-control study. Serum samples from all groups were analyzed for HCV. Endocan was measured by enzyme-linked immunosorbent assays, and the expression levels of circulating miRNA 9-3p were measured by real-time quantitative reverse transcriptase PCR.

Results: The levels of circulating miRNA 9-3p were significantly lower in the HCC group compared to the chronic liver disease (P < 0.001) and control (P < 0.001) groups, while levels in the chronic liver disease were significantly lower than those in the control group (P < 0.001). The levels of serum endocan were significantly higher in the HCC group compared to the chronic liver disease (P < 0.001) and control (P < 0.001) groups. Moreover miRNA 9-3p and endocan performed better than α-fetoprotein in discriminating HCC patients from cirrhosis and healthy patients. The levels of miRNA 9-3p were significantly inversely correlated to vascular invasion (P = 0.002), stage of advancement of Barcelona Clinical Liver Cancer (P < 0.001) and the metastatic site (P < 0.001) of the HCC group.

Conclusion: Circulating miRNA 9-3p and endocan can be used as novel biomarkers for the early diagnosis of HCV-related HCC.