Abstract
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.
Highlights
Worldwide, bladder cancer accounts for approximately 3.0% of all malignancies
As Tumor mutation burden (TMB) is reported to be a biomarker for immunotherapy and E1A binding protein P300 (EP300) mutation was associated with an increased TMB, we further investigated the relation of EP300 mutation and immune response
We found that EP300 was frequently mutated in both The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts, and its mutation was associated with higher TMB and favorable clinical prognosis
Summary
Bladder cancer accounts for approximately 3.0% of all malignancies. Approximately 70% of bladder cancer patients present with the non-muscle invasive type, as many as half of them experience disease recurrence after receiving transurethral resection, and up to quarter of them progress to muscleinvasive bladder cancer (MIBC) after repeated recurrences [2]. Approximately 30% of patients have muscle invasive disease at the time of initial diagnosis, and radical cystectomy is the current standard of care [3]. Systemic chemotherapy using cisplatin-based regimens has been the predominant treatment for metastatic urothelial carcinoma (mUC). Approximately 50% of patients with mUC are ineligible to receive cisplatin due to severe adverse effects [5]. For patients for whom first-line chemotherapy is not successful, there is an urgent need to find a novel treatment option to improve clinical outcomes
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