J Cancer 2018; 9(22):4108-4116. doi:10.7150/jca.27281 This issue
1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
*These authors contributed equally to this work.
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.
Keywords: clear cell renal cell carcinoma, BAP1, mutation, bioinformatics