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

Abstract:

:Purpose: Aim of this study was to comprehensively analyze BRCA1-associated protein-1 (BAP1) somatic mutation in clear cell renal cell carcinoma (ccRCC) and explore potential therapeutic pathways and molecules. Patients and methods: In this study, we analyzed 445 ccRCC cases from The Cancer Genome Atlas (TCGA). Comprehensive analysis including survival, transcriptome and methylation between BAP1 mutated and wild-type cases was performed using bioinformatics tools in silico. Pathways and molecules related to BAP1 mutation were analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) and protein-protein interaction (PPI) network. Results:BAP1 mutated ccRCC patients had a worse overall survival (OS) and disease free survival (DFS) than BAP1 wild-type patients. We found 583 up-regulated and 1216 down-regulated different expressed genes (DEGs) in BAP1 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, CAD, TSPO, CTNNB1 and MAPK3 were top hub genes selected using PPI network analysis. Finally, BAP1 mutation had a strong correlation with CpG island methylator phenotype (CIMP). Conclusion: Our study provides a comprehensive understanding of BAP1 functional somatic mutation in ccRCC patients. Several hub genes like CAD and TSPO may become potential therapeutic targets.

journal_name

J Cancer

journal_title

Journal of Cancer

authors

Jin S,Wu J,Zhu Y,Gu W,Wan F,Xiao W,Dai B,Zhang H,Shi G,Shen Y,Zhu Y,Ye D

doi

10.7150/jca.27281

subject

Has Abstract

pub_date

2018-10-18 00:00:00

pages

4108-4116

issue

22

issn

1837-9664

pii

jcav09p4108

journal_volume

9

pub_type

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