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

摘要/Abstract

摘要： 目的：探讨肿瘤突变负荷（TMB）在肌层浸润性膀胱癌（MIBC）预后评估中的价值。方法：从TCGA数据库下载MIBC测序数据，结合临床数据分析TMB在MIBC中的临床意义，从TMB分组中识别出差异表达的免疫相关基因进行预后分析；另外采用非负矩阵分解CIBERSORT算法确定免疫细胞与TMB亚型之间的相关性。结果：纳入的375例MIBC患者样品中单核苷酸多态性（SNP）和C > T是最常见的错义突变；TP53、TTN、KMT2D、MUC16、ARID1A基因的突变率较高；与低TMB组MIBC患者相比，高TMB组的患者预后较好（P < 0.01）；以KIR2DL4、IL1RL1、SSTR5构建的COX回归模型中低风险组MIBC患者较高风险组预后更佳，曲线下面积（ROC）为0.71；与正常膀胱组织相比，高TMB组的CD8⁺ T细胞、活化的CD4⁺ T细胞、嗜酸性粒细胞表达较高，而在低TMB组中记忆B细胞及未活化的肥大细胞表达比例较高（P < 0.05）。结论：TMB较高的MIBC患者可能在免疫治疗中获得较好的预后，TMB具有预测肿瘤免疫治疗疗效的潜在应用价值；还发现了不同组分的免疫细胞在TMB分组的MIBC肿瘤微环境中存在表达差异。

关键词: 肌层浸润, 膀胱癌, 肿瘤突变负荷, TCGA, 预后

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

中图分类号:

R730.2

石海林, 何天基, 刘峰, 蔡孟会, 葛波. 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[J]. 癌变·畸变·突变, 2020, 32(6): 430-437,443.

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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