Research Paper Volume 12, Issue 3 pp 2132—2141

EP300 mutation is associated with tumor mutation burden and promotes antitumor immunity in bladder cancer patients

Gongmin Zhu1, *, , Lijiao Pei2, *, , Yuan Li3, , Xin Gou1, ,

  • 1 Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 2 The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
  • 3 Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
* Equal contribution

Received: October 10, 2019       Accepted: January 2, 2020       Published: February 3, 2020
How to Cite

Copyright: © 2020 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Bladder cancer is a leading cause of morbidity and mortality worldwide. Currently, immunotherapy has become a worthwhile therapy for bladder cancer. Tumor mutation burden (TMB) has been regarded as the most prevalent biomarker to predict immunotherapy. Bladder cancer is reported to have the third highest mutation rate. However, whether these gene mutations are related to TMB and immune response remain unknown. In this study, we downloaded somatic mutation data of bladder cancer from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets, and found 11 frequently mutated genes were covered by both two cohorts including FGFR3, TTN, XIRP2, CREBBP, PIK3CA, TP53, MUC16, EP300 (E1A binding protein P300), ARID1A, ERBB2, and KDM6A. Among them, EP300 mutation was associated with higher TMB and indicated a favorable clinical prognosis. Furthermore, based on Gene set enrichment analysis (GSEA) and CIBERSORT algorithm, we observed that EP300 mutation upregulated signaling pathways involved in immune system and enhanced antitumor immune response. In conclusion, EP300 is frequently mutated in bladder cancer, and its mutation is associated with increased TMB and promotes antitumor immunity, which may serve as a biomarker to predict immune response.


EP300: E1A binding protein P300; TMB: tumor mutation burden; TCGA: The Cancer Genome Atlas; ICGC: International Cancer Genome Consortium; GSEA: Gene set enrichment analysis; MIBC: muscle-invasive bladder cancer; mUC: metastatic urothelial carcinoma; Mb: megabase; NES: normalized enrichment score; KAT: histone acetyltransferase; CBP: cAMP response element binding protein; Foxp3: Forkhead box P3.