Characterization of Serum Protein Biomarkers for Diagnosis of Hepatocellular Carcinoma (HCC)

Abstract

Hepatocellular carcinoma contributes excessively to the global burden of cancer. HCC affects developing countries due to poor healthcare systems and recently its incidence is on the rise globally. In Pakistan, HCC occurs on average in 7.6 persons per 100,000 annually. Moreover, HCC is associated with Hepatitis C, another prevalent infection in Pakistan, which contributes to about 60-70% of HCC incidence here. Poorly developed healthcare systems in the Third World countries result in late detection of HCC since it is diagnosed via Imaging techniques like MRI, Ultrasound and histopathology which often require expensive, healthcare systems. Significant research is being done to develop novel HCC biomarkers for its early detection of the disease. These include development of biomarkers based on transcriptomic and proteomic profiles of HCC patients. Circulating proteins can therefore pose an opportunity for biomarker development of HCC as these can be easily detected in the body fluids among which blood serum is the ideal choice. There is a need to develop blood-based serum biomarkers for easy, non invasive, and early detection of HCC. Alpha Fetoprotein (AFP) has been used to diagnose HCC in conjunction with imaging techniques, but it has very less clinical utility. In recent years, research has focused on other multiple circulating proteins as biomarker candidates for HCC detection. In this study, blood serum was used to validate 4 novel protein biomarker candidates previously predicted in our study via a bioinformatics pipeline (Awan et al., 2015). Proteins namely C8A, SERPINC1, HSD11B1 and MBL2 were checked in the serum of 150 HCC patients and compared with the AFP levels via quantitative ELISA. Among these, C8A poses significant biomarker potential with 85.33% sensitivity and 100% specificity values and SERPINC1 showed 80.67% sensitivity and 68% specificity whereas MBL2 and HSD11B1 did not show significant biomarker potential. These results were then confirmed via Western blot of selected serum samples of C8A. Conclusively, C8A showed excellent potential to serve as a circulating blood-based protein biomarker for detection of HCC. SERPINC1 also showed moderate results but not better than AFP