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

被引：18

作者：

Jin, Shengming ^{[1
,2
]}

Wu, Junlong ^{[1
,2
]}

Zhu, Yao ^{[1
,2
]}

Gu, Weijie ^{[1
,2
]}

Wan, Fangning ^{[1
,2
]}

Xiao, Wenjun ^{[1
,2
]}

Dai, Bo ^{[1
,2
]}

Zhang, Hailiang ^{[1
,2
]}

Shi, Guohai ^{[1
,2
]}

Shen, Yijun ^{[1
,2
]}

Zhu, Yiping ^{[1
,2
]}

Ye, Dingwei ^{[1
,2
]}

机构：

[1] Fudan Univ, Dept Urol, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai 200032, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China

来源：

JOURNAL OF CANCER | 2018年 / 9卷 / 22期

基金：

中国国家自然科学基金;

关键词：

dear cell renal cell carcinoma; BAP1; mutation; bioinformatics; TRANSLOCATOR PROTEIN TSPO; EXPRESSION; PBRM1; SETD2; PROGNOSIS; DATABASE; OUTCOMES; TARGETS; MAPK3/1; MARKER;

D O I：

10.7150/jca.27281

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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: BAPI 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 Rapt 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.

引用

页码：4108 / 4116

页数：9