Tissue Biomarkers in the Early Detection of Hepatocellular Carcinoma among Egyptian Patients with Chronic Hepatitis C: A Possible Genetic Profile

Abstract

Background and Study Aims: Gene expression of biomarkers involved in hepatocarcinogensis could be used for the early diagnosis of hepatocellular carcinoma (HCC). Aim: To evaluate the hepatocyte expression of Glypican-3 (GPC-3), paternally expressed gene 10 (PEG-10), Midkine (MDK), Serpin peptidase inhibitor (SERPINI1), and Ubiquinol-cytochrome (QP-C) which can represent a possible genetic profile among hepatitis C virus (HCV)-related HCC patients. Patients and Methods: This prospective study was conducted on 70 Egyptian patients with HCV-related chronic liver disease and HCC patients. Patients were categorized into chronic HCV group (n=25), post-HCV cirrhosis group (n=24), HCC group (n=21) in addition to 7 healthy individuals who were candidates for living-donor related transplantation. Liver tissue obtained from all patients was subjected to total RNA extraction, reverse transcription of extracted RNA into cDNA and finally tissue expression of GPC-3, MDK, PEG-10, SERPINI1 and QP-C by qRT-PCR was assessed in each group. Results: A significant increase in hepatocyte expression of GPC-3, MDK, SERPINI1, and QP-C was detected in cancerous compared to non-cancerous liver tissue; in contrast, PEG-10 was significantly expressed in chronic HCV patients. The ROC curves was able to identify best cutoff values, sensitivity and specificity for GPC-3 (7.26, 81%, 58%), SERPINI1 (0.16, 80%, 70%), MDK (3.8, 60%, 70%) and QP-C (0.45, 65%, 79%) respectively. There was no significant correlation between the tissue expression of these biomarkers and the size of hepatic focal lesion or AFP levels. Conclusion: Hepatocyte expression of GPC-3, MDK, SERPINI1, and QP-C could represent a potential genetic profile for the early detection of HCC.