Tissue Biomarkers in the Early Detection of Hepatocellular Carcinoma among Egyptian Patients with Chronic Hepatitis C: A Possible Genetic Profile
Hassan El-Garem
Endemic Medicine and Hepatology Department Faculty of Medicine, Cairo University, Egypt.
Hanan Abdel- HafezB *
Endemic Medicine and Hepatology Department Faculty of Medicine, Cairo University, Egypt.
Ahmed Foaud
Endemic Medicine and Hepatology Department Faculty of Medicine, Cairo University, Egypt.
Wafaa Al Akel
Endemic Medicine and Hepatology Department Faculty of Medicine, Cairo University, Egypt.
Mohey EldienAtia
Tropical Department, Theodor Bilharz Research Institute, Egypt.
Mona Salah
Clinical Pathology Department,Faculty of Medicine, Cairo University, Egypt.
Hany Khatteb
Pathology Department, Faculty of Medicine, Cairo University, Egypt.
Heba Osman
Endemic Medicine and Hepatology Department Faculty of Medicine, Cairo University, Egypt.
Khaled Ragab
Tropical Department, Theodor Bilharz Research Institute, Egypt.
Naglaa Zayed
Endemic Medicine and Hepatology Department Faculty of Medicine, Cairo University, Egypt.
*Author to whom correspondence should be addressed.
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.
Keywords: GPC-3, MDK, SERPINI1, PEG, QP-C, HCC, HCV, Egypt