ONCOmmunity

Discovering therapeutic protein targets for muscle invasive bladder cancer by proteomic data analysis.

By: Samira Bahrami, Bahram Kazemi, Hakimeh Zali, Peter C Black, Abbas Basiri, Amirhossein Sahebkar

Biotechnology Department, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran. Iran.
2019-04-04; doi: 10.2174/1874467212666191016124935

Abstract

Background

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 the solid tumors. Selecting a suitable target is the most critical step for this strategy.

Objective

The aim of this study is to detect therapeutic cell surface antigen targets in bladder cancer using data obtained by proteomic studies.

Methods

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 protein 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.

Results

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), cadherin 2 (CDH2). Monoclonal antibodies against these proteins or their inhibitors were used for the treatment of different cancers in preclinical and clinical trials.

Conclusion

These monoclonal antibodies and inhibitor molecules and also their combination can be used for treatment of bladder cancer.