Significance of TP53 mutation in bladder cancer disease progression and drug selection

PeerJ

article

Guang Wu¹  Fei Wang¹  Kai Li¹  Shugen Li¹  Chunchun Zhao¹  Caibin Fan¹  Jianqing Wang¹ 

[1] The Affiliated Suzhou Hospital of Nanjing Medical University

关键词: Bladder cancer;    TP53 mutation;    TCGA;    RNA sequencing;    Bioinformatics analysis;    Drug selection;   

DOI  :  10.7717/peerj.8261

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Background The tumor protein p53 (TP53) mutant is one of the most frequent mutant genes in bladder cancer. In this study, we assessed the importance of the TP53 mutation in bladder cancer progression and drug selection, and identified potential pathways and core genes associated with the underlying mechanisms. Methods Gene expression data used in this study were downloaded from The Cancer Genome Atlas and cBioportal databases. Drug sensitivity data were obtained from the Genomics of Drug Sensitivity in Cancer. We did functional enrichment analysis by gene set enrichment analysis (GSEA) and the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results We found the TP53 mutation in 50% of bladder cancer patients. Patients with the TP53 mutation were associated with a lower TP53 mRNA expression level, more advanced tumor stage and higher histologic grade. Three drugs, mitomycin-C, doxorubicin and gemcitabine, were especially more sensitive to bladder cancer with the TP53 mutation. As for the mechanisms, we identified 863 differentially expressed genes (DEGs). Functional enrichment analysis suggested that DEGs were primarily enriched in multiple metabolic progressions, chemical carcinogenesis and cancer related pathways. The protein–protein interaction network identified the top 10 hub genes. Our results have suggested the significance of TP53 mutation in disease progression and drug selection in bladder cancer, and identified multiple genes and pathways related in such program, offering novel basis for bladder cancer individualized treatment.

【 授权许可】

CC BY