基于TCGA数据库分析肿瘤突变负荷在肌层浸润性膀胱癌预后评估中的价值

doi:10.3969/j.issn.1004-616x.2020.06.004

Abstract

Abstract: OBJECTIVE: To access the TCGA database for tumor mutation burden (TMB) in muscle-invasive bladder cancers (MIBC) and to investigate their prognostic values. METHODS: MIBC sequencing data from the TCGA database and clinically significant TMB in the MIBC were used to determine their prognostic values that were related to differentially expressed immune-related genes. In addition,non-negative matrix decomposition CIBERSORT algorithm was used to determine correlations between immune cells and TMB subtypes. RESULTS: Our data indicate that single nucleotide polymorphisms (SNP) and C > T were the most common missense mutations in the 375 MIBC patients. In addition,mutation rates of TP53,TTN,KMT2D,MUC16 and ARID1A genes were elevated. Among the MIBC patients,those in the high TMB group had better prognosis (P < 0.01). In the COX regression model which was constructed by KIR2DL4,IL1RL1 and SSTR5,the low-risk group of MIBC patients compared with the higher risk group had a better prognosis,with the ROC of 0.71. In contrast with normal bladder tissues,expression of CD8⁺ T cells,activated CD4⁺ T cells and eosinophils was higher in the high TMB group,while expression of memory B cells and non-activated mast cells was higher in the low TMB group (P < 0.05). CONCLUSION: MIBC patients with higher TMB may have better prognosis in immunotherapy,and TMB has potential clinical application in predicting tumor immunotherapy. In addition,different components of immune cells were found to be differentially expressed in the TMB subgroup MIBC microenvironment.

Key words: muscle-invasive, bladder cancer, tumor mutation burden, TCGA, prognosis

CLC Number:

R730.2

SHI Hailin, HE Tianji, LIU Feng, CAI Menghui, GE Bo. Prognostic value of TCGA-database mutation burden in muscle-invasive bladder cancers[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 430-437,443.

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Prognostic value of TCGA-database mutation burden in muscle-invasive bladder cancers

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