LAUSR

Identification of events leading to HCC progression is essential for understanding its pathophysiology. Present study was designed to identify differentially expressed proteins in serum of HCC-bearing rats vis-a-vis controls during cancer initiation, progression and tumorigenesis. HCC was chemically induced by administering N-Nitrosodiethylamine and 2-aminoacetylfluorine to male Wistar rats. Carcinogen administration caused inflammation leading to liver injury and HCC development. Liver inflammation was confirmed by increase in levels of IL-6 and TNF-α in carcinogen treated rats. The 2D-Gel Electrophoresis and MALD-TOF-MS analysis identified several differentially expressed proteins in serum of HCC-bearing animals vis-a-vis age-matched controls. We report significant elevation in expression of two of these proteins, namely, A-Raf and fatty acid 2-hydroxylase (FA2H), at early stage of HCC initiation, during its progression and at tumor stage. The elevated-expression was validated by Western blot analysis. Real-time PCR analysis of mRNA isolated from tumor tissues confirmed up-regulation of their transcripts. Further, we validated our experimental data in serum of clinically confirmed liver cancer patients. Furthermore, we have identified a novel HCC-specific network among these proteins and their interactors representing a complex inter-relationship between signaling pathways that may regulate HCC development. The study suggests that FA2H and A-Raf play major role in HCC progression .