Mining TCGA database for tumor mutation burden and their clinical significance in bladder cancer
Mining TCGA database for tumor mutation burden and their clinical significance in bladder cancer
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DOI：
10.1042/bsr20194337
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发表时间：
2020-04-21
影响因子：
4
通讯作者：
Liao, Guodong
中科院分区：
文献类型：
--
作者：
Lv, Jia;Zhu, Yongze;Liao, Guodong
背景：膀胱癌是全球第九大常见癌症，与高发病率和高死亡率有关。肿瘤突变负荷(TMB)是一种以微卫星不稳定性为特征的新的肿瘤生物标志物。TMB已被描述为预测肿瘤行为和免疫治疗反应的有力指标。方法：从肿瘤基因组图谱(TCGA)获得443例膀胱癌标本，分析TMB的突变类型、TMB值和预后价值。从TMB分组中鉴定出差异表达基因(DEG)。进行功能分析以评估前30个核心基因的预后价值。结果：单核苷酸多态(SNP)和C>；T是最常见的错义突变，TP53、TTN、KMT2D也有较高的突变率。TMB升高的膀胱癌患者预后较好。富集分析表明，它们参与了P13K-Akt信号通路、细胞因子-细胞因子受体相互作用和RAS信号通路的调节。HUB基因ADRA2A、CXCL12、S1PR1、ADAMTS9、F13A1和SPON1的高表达与总存活率低相关。T细胞CD8、T细胞CD4记忆激活、NK细胞静息和肥大细胞静息的免疫细胞组成有显著差异。结论：本研究为膀胱癌患者TMB的预测及其临床意义提供了全面系统的分析。此外，该研究还为膀胱癌的免疫治疗提供了更多的预后信息和机会。
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. CIBER-SORT 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.