Identification Of Molecular Phenotypes Of Urothelial Carcinoma Of The Bladder
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Date
2017
Department
Computer Science and Bioinformatics Program
Program
Master of Science
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This item is made available by Morgan State University for personal, educational, and research purposes in accordance with Title 17 of the U.S. Copyright Law. Other uses may require permission from the copyright owner.
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Abstract
The prevalence of bladder cancer is one of the common causes of high mortality in the world. Advances in the identification of genomic alterations that lead to urothelial carcinoma of the bladder (BCa), and recent approval of immune check point inhibitors have provided durable systemic treatment options for patients with advanced or metastatic bladder cancer. In view of positive clinical responses to cabozantinib an immunotherapy drug in a recent phase II clinical trial at the National Cancer Institute, a broad panel of putative cabozantinib targeted receptor tyrosine kinases (RTKs) was examined to identify new therapeutic targets. Alterations in The Cancer Genome Atlas (TCGA) BCa datasets revealed that patients with muscle invasive disease had at least one RTK gene amplified and/or mRNA upregulated. Furthermore, many TCGA patient samples displayed both RTK and cognate ligand overexpression, specifically GAS6/AXL, MST1/MST1R and CSF1/CSF1R pathways, creating the potential for autocrine RTK signaling to drive BCa oncogenesis in these patients. Recent studies on other bladder cancer provisional datasets have identified groups of receptor tyrosine kinases, DNA repair genes (DNADR) and transcriptional activators in the epithelial mesenchymal transition (EMT) pathway. The goal of this research is to identify the cohorts that have these genetic alterations in these groups (RTK, EMT, DNADR) and observe the impact on overall and disease-free survival on those with altered and unaltered genes. The results highlighted that alterations to EMT transcriptional activators had the most significant impact on overall and disease-free survival of the bladder cancer patients, potentially highlighting the pathway as a potential biomarker for drug targeted therapy