Comprehensive Analysis of BAP1 Somatic Mutation in Clear Cell Renal Cell Carcinoma to Explore Potential Mechanisms in Silico

• Published in: Journal of Cancer 2018-01, Vol.9 (22), p.4108-4116
• Main Authors: Jin, Shengming, Wu, Junlong, Zhu, Yao, Gu, Weijie, Wan, Fangning, Xiao, Wenjun, Dai, Bo, Zhang, Hailiang, Shi, Guohai, Shen, Yijun, Zhu, Yiping, Ye, Dingwei
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1837-9664; 1837-9664
• DOI: 10.7150/jca.27281

Aim of this study was to comprehensively analyze BRCA1-associated protein-1 ( ) somatic mutation in clear cell renal cell carcinoma (ccRCC) and explore potential therapeutic pathways and molecules. In this study, we analyzed 445 ccRCC cases from The Cancer Genome Atlas (TCGA). Comprehensive analysis including survival, transcriptome and methylation between mutated and wild-type cases was performed using bioinformatics tools . Pathways and molecules related to mutation were analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) and protein-protein interaction (PPI) network. mutated ccRCC patients had a worse overall survival (OS) and disease free survival (DFS) than wild-type patients. We found 583 up-regulated and 1216 down-regulated different expressed genes (DEGs) in mutated tumors. Up-regulated DEGs were enriched in molecular functions and biological processes like protein binding, protein transport and ubiquitin protein ligase binding. Down-regulated DEGs were enriched in pathways like Rap1 signaling pathway, Notch pathway and altered molecular functions like metal ion binding and ubiquitin-protein transferase activity. Furthermore, and were top hub genes selected using PPI network analysis. Finally, mutation had a strong correlation with CpG island methylator phenotype (CIMP). Our study provides a comprehensive understanding of functional somatic mutation in ccRCC patients. Several hub genes like and may become potential therapeutic targets.