PROTEOMICS IDENTIFICATION AND CHARACTERIZATION OF NOVEL BIOMARKERS ASSOCIATED WITH RECURRENCE OF HEPATOCELLULAR CARCINOMA

Abstract

HEPATOCELLULAR CARCINOMA (HCC) IS ONE OF THE MOST DEADLY CANCERS IN THE WORLD DUE TO THE HIGH RECURRENCE RATE. IDENTIFICATION OF BIOMARKERS THAT CAN PREDICT THE RISK OF RECURRENCE MAY AID IN CLINICAL MANAGEMENT OF HCC PATIENTS. HENCE, IN THE DISCOVERY PHASE, WE EMPLOYED QUANTITATIVE PROTEOMICS TO IDENTIFY DIFFERENTIALLY EXPRESSED PROTEINS IN THE HCC TISSUES OF EARLY RECURRENCE AND RECURRENCE-FREE PATIENTS. AN INCREASED UPREGULATION OF DNPH1 WAS OBSERVED IN THE TUMOURS OF EARLY RECURRENCE PATIENTS, WHICH WAS VALIDATED USING SWATH-MS AND WESTERN BLOT. SUBSEQUENTLY, THE ROLE OF DNPH1 IN HCC METASTASIS WAS EVALUATED BY IN VITRO ASSAYS. KNOCKDOWN OF DNPH1 RESULTED IN DECREASED METASTATIC POTENTIAL OF HEP3B CELLS. PROTEOMICS STUDY ON DNPH1 KNOCKDOWN CELLS REVEALED CHANGES IN EXPRESSION OF PROTEINS IMPLICATED IN METASTASIS, REDOX MODULATION, LIPID METABOLISM AND ELECTRON TRANSPORT CHAIN COMPLEX FORMATION. THESE FINDINGS IMPLICATE DNPH1 AS A POTENTIAL TARGET FOR PREVENTION OF HCC RECURRENCE