Abstract
Background: Bladder cancer is the ninth most-common cancer worldwide and it is associated with high morbidity and mortality. Tumor mutational burden (TMB) is an emerging biomarker in cancer characterized by microsatellite instability. TMB has been described as a powerful predictor of tumor behavior and response to immunotherapy.Methods: A total of 443 bladder cancer samples obtained from The Cancer Genome Atlas (TCGA) were analyzed for mutation types, TMB values, and prognostic value of TMB. Differentially expressed genes (DEGs) were identified from the TMB groupings. Functional analysis was performed to assess the prognostic value of the first 30 core genes. CIBERSORT algorithm was used to determine the correlation between the immune cells and TMB subtypes.Results: Single nucleotide polymorphism (SNP) and C>T were reported as the most common missense mutations and we also identified a high rate of mutations in TP53, TTN, KMT2D. Bladder cancer patients with high TMB showed a better prognosis. Enrichment analysis of the DEGs revealed that they were involved in the regulation of the P13K-Akt signaling pathway, cytokine–cytokine receptor interaction, and Ras signaling pathway. The high expression of hub genes ADRA2A, CXCL12, S1PR1, ADAMTS9, F13A1, and SPON1 was correlated with poor overall survival. Besides, significant differences in the composition of the immune cells of T cells CD8, T cells CD4 memory activated, NK cells resting and Mast cells resting were observed.Conclusions: The present study provides a comprehensive and systematic analysis of the prediction of TMB in bladder cancer and its clinical significance. Also, the study provides additional prognostic information and opportunities for immunotherapy in bladder cancer.
Highlights
Bladder cancer, the ninth most-common malignancy worldwide with an estimated 356000 new cases and 145000 deaths annually, has a propensity to relapse, requiring lifelong monitoring after diagnosis [1,2]
The findings revealed that missense mutations, Single nucleotide polymorphism (SNP), and C>T mutation were more common, with the highest mutation frequency being 3398 (Figure 1A)
Based on the MutSigCV algorithm, the waterfall diagram revealed the integration status of somatic mutations in The Cancer Genome Atlas (TCGA) bladder cancer, and the results showed that the somatic mutations of TP53, TTN, KMT2D, ARID1A, MUC16, PIK3CA, and RB1 (P
Summary
The ninth most-common malignancy worldwide with an estimated 356000 new cases and 145000 deaths annually, has a propensity to relapse, requiring lifelong monitoring after diagnosis [1,2]. Poor prognosis in muscle-invasive bladder cancer is reported with 85% of the patients dying within 2 years without treatment [5]. The use of immunotherapy in the treatment of muscle-invasive and metastatic bladder cancer has shown great potential in clinical application [6]. Bladder cancer is the ninth most-common cancer worldwide and it is associated with high morbidity and mortality. Expressed genes (DEGs) were identified from the TMB groupings. Functional analysis was performed to assess the prognostic value of the first 30 core genes. Bladder cancer patients with high TMB showed a better prognosis. The high expression of hub genes ADRA2A, CXCL12, S1PR1, ADAMTS9, F13A1, and SPON1 was correlated with poor overall survival. Conclusions: The present study provides a comprehensive and systematic analysis of the prediction of TMB in bladder cancer and its clinical significance. The study provides additional prognostic information and opportunities for immunotherapy in bladder cancer
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