Discovering Therapeutic Protein Targets for Bladder Cancer Using Proteomic Data Analysis.

Abstract

Bladder cancer accounts for almost 54% of urinary system cancer and is the second most frequent cause of death in genitourinary malignancies after prostate cancer. About 70% of bladder tumors are non-muscle-invasive, and the rest are muscle-invasive. Recurrence of the tumor is the common feature of bladder cancer. Chemotherapy is a conventional treatment for MIBC, but it cannot improve the survival rate of these patients sufficiently. Therefore, researchers must develop new therapies. Antibody-based therapy is one of the most important strategies for the treatment of solid tumors. Selecting a suitable target is the most critical step for this strategy. The aim of this study is to detect therapeutic cell surface antigen targets in bladder cancer using data obtained by proteomic studies. Isobaric tag for relative and absolute quantitation (iTRAQ) analysis had identified 131 overexpressed proteins in baldder cancer tissue and reverse-phase proteomic array (RPPA) analysis had been done for 343 tumor tissues and 208 antibodies. All identified proteins from two studies (131+208 proteins) were collected and duplicates were removed (331 unique proteins). Gene ontology study was performed using gene ontology (GO) and protein analysis through evolutionary relationships (PANTHER) databases. The Human Protein Atlas database was used to search the protein class and subcellular location of membrane proteins obtained from the PANTHER analysis. Membrane proteins that could be suitable therapeutic targets for bladder cancer were selected. These included: Epidermal growth factor receptor (EGFR), Her2, Kinase insert domain receptor (KDR), Heat shock protein 60 (HSP60), HSP90, Transferrin receptor (TFRC), Activin A Receptor Like Type 1 (ACVRL1), and cadherin 2 (CDH2). Monoclonal antibodies against these proteins or their inhibitors were used for the treatment of different cancers in preclinical and clinical trials. These monoclonal antibodies and inhibitor molecules and also their combination can be used for the treatment of bladder cancer.