EVALUATION OF bcl-2 AND TRANSFORMING GROWTH FACTOR ALPHA ONCOPROTEINS IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION: IMPACT ON HEPATOCELLULAR CARCINOMA
Mahmoud I. Hassan1, Amal Abou El-Fadle2, Gamal M. Kenawy2, Fayda I. Abdel Motaleb1 and Fatma M. Abdel Salam3
1Oncology Diagnostic Unit, Faculty of Medicine Ain Shams University,
2Medical Biochemistry and 3Tropical Medicine Departments, Benha Faculty of Medicine, Zagazig University
Persistent hepatitis C virus (HCV) infection is associated with the development of human hepatocellular carcinoma (HCC), although the mechanism of HCV-related hepatocarcinogenesis remains unclear. bcl-2 oncoprotein can prolong cell survival by blocking apoptosis without affecting cellular proliferation. Transforming growth factor alpha (TGF-α) is alleged to play a role in malignant progression as well as normal cell growth in an autocrine manner. The present study was carried out to investigate the kinetics of bcl-2, TGF-α and alpha-fetoprotein (AFP) release in sera, ascitic fluid and liver tissue from chronically infected HCV infected patients and those with HCC. The impact of these biomarkers on the development of HCC was also investigated. The obtained results revealed that serum bcl-2 was significantly higher (p <0.001) in HCV and HCC as compared to the healthy control group. Moreover, serum bcl-2 levels in HCC were significantly higher (p <0.001) than in HCV patients. This may suggest that the antiapoptotic oncoprotein bcl-2 may provide hepatocytes with sufficient time in the inflamed tissue to accumulate the specific gene mutations that culminate cancer. This work showed that serum TGF-β level was significantly higher in HCV and HCC patients (p <0.001) as compared to the healthy control adults. However, there was non significant difference in serum TGF-β level in HCV patients as compared to those with HCC. This finding could suggest that TGF-β might be the primary marker to start the process of carcinogenesis, however, higher levels of TGF-α may not be needed to the progress of malignancy. Serum TGF-β levels were significantly higher (p <0.05) in HCV patients with liver cirrhosis than HCV without cirrhosis. This might suggest that the hepatocyte regeneration occurring in cirrhosis could contribute to the higher serum TGF-β levels in HCV patients with liver cirrhosis. The sensitivity and specificity to detect HCC in HCV patients were 62.5% and 90.9% for serum bcl-2; 37.5% and 68.2% for serum TGF-α; 56.3% and 90.1% for AFP. In conclusion, bcl-2 oncoprotein overexpression in hepatocytes in HCV suggests that the available mechanism of apoptosis may be suppressed by bcl-2. The increased expression of bcl-2 oncoprotein in HCC, by its antiapoptotic action, is essential for carcinogenesis to proceed to malignancy. Serum bcl-2 may be helpful for diagnosis of HCC developing in HCV patients. Although the increased expression of bcl-2 oncoprotein in HCC suggests that bcl-2 may be involved in hepatocarcinogenesis, further investigations through molecular techniques is necessary, in order to define the exact role of apoptosis-related genes in this neoplastic process.