标题:基于TCGA数据库研究肿瘤突变负荷与膀胱癌的相关性
作者:罗雪颜,王光明 大理大学第一附属医院基因检测中心,云南 大理 671000
卷次:
2022年33卷7期
【摘要】 目的 从TCGA数据库中探究肿瘤突变负荷(TMB)与膀胱癌的相关性,有助于膀胱癌免疫机制的深入研究,为膀胱癌的免疫治疗提供更多的预测信息和机会。方法 对从TCGA数据库获取的共443例膀胱癌样本进行突变分析、依据TMB表达高低进行分组,并分析高低TMB组与临床相关性、预后值以及与免疫细胞的关联性。差异表达基因(DEGs)从TMB分组中识别而来,再进行功能分析以评估差异表达基因的潜在生物学功能。22个免疫细胞与TMB亚型的相关性的分析采用CIBERSORT算法推导。结果 443例膀胱癌样本的突变类型中最多的是错义突变,变体类型最常见的是单核苷酸多态性(single nucleotide polymorphism,SNP)。突变类型中单核苷酸变异(single nucleotide variant,SNV)以C>T突变为58 755,占最大部分,其次是C>G突变为29 935。研究发现膀胱癌中突变率居前三的基因分别是TP53、TTN、KMT2D,突变率分别为47%、40%、26%。其中存在互斥现象的突变基因是 TP53和 FGFR3,TP53与突变的 RB1基因存在共现。出现共突变现象的是 TTN基因与 FAT4、ATM、MACF1、HMCN1、PIK3CA和MUC16基因。KMT2D基因和KMT2C基因存在共突变。在膀胱癌患者生存期比较中,高TMB表达组明显高于低TMB组,差异具有统计学意义(P=0.006)。预测高TMB组膀胱癌患者预后较好。此外,TMB与性别(P=0.016)和肿瘤分级(P<0.001)具有相关性。差异表达基因富集分析在参与调控肾素-血管紧张素系统、P13K-Akt信号通路、细胞因子-细胞因子受体相互作用和Ras信号通路等方面表现显著。此外,观察到CD8+ T细胞、记忆激活CD4+T细胞、静息的NK细胞和肥大细胞的免疫细胞组成在高低TMB组中表达存在差异。结论 本研究通过探讨TMB与膀胱癌的相关性,发现TMB较高的膀胱癌患者可能在免疫治疗中获得较好的预后。CD8+T细胞和记忆激活CD4+T细胞亚群在高TMB组中表现出比较高的浸润丰度。
【关键词】 膀胱癌;TCGA数据库;肿瘤突变负荷;肿瘤微环境;免疫细胞浸润;预后
【中图分类号】 R737.14 【文献标识码】 A 【文章编号】 1003—6350(2022)07—0837—08
Correlation between tumor burden and bladder cancer based on TCGA database.
LUO Xue-yan, WANGGuang-ming. Gene Testing Center, the First Affiliated Hospital of Dali University, Dali 671000, Yunnan, CHINA
【Abstract】 Objective To explore the correlation between tumor mutation load (TMB) and bladder cancerbased on TCGA database, in order to explore the immune mechanism of bladder cancer and provide more prediction op-portunities for immunotherapy of bladder cancer in the future. Methods A total of 443 cases of bladder cancer samplesobtained from TCGA database were analyzed for mutation analysis. They were grouped according to TMB expression,and the correlation between high and low TMB groups with clinical, prognostic value analysis and correlation with im-mune cells were analyzed. Differentially expressed genes (DEGs) were identified from the TMB grouping, and function-al analysis was performed to assess the potential biological function of the differentially expressed genes. The correlationanalysis between 22 immune cells and TMB subtypes was deduced by CIBERSORT algorithm. Results In 443 casesof bladder cancer, missense mutation was the most common mutation type, and single nucleotide polymorphism (SNP)was the most common variant type. In mutation type, single nucleotide variant (SNV) were mostly C>T (58 755), fol-lowed by C>G (29 935). The genes with top three mutation rates in bladder cancer were TP53, TTN and KMT2D, withmutation rates of 47%, 40%, and 26%, respectively. Among them, the mutated genes of TP53 and FGFR3 had mutual ex-clusion, while TP53 co-existed with the mutated RB1 gene. Co-mutation phenomenon was found in TTN gene andFAT4, ATM, MACF1, HMCN1, PIK3CA and MUC16 genes. KMT2D and KMT2C also showed co-mutation. The sur-vival of bladder cancer patients in the high TMB expression group was significantly higher than that in the low TMB ex-pression group, with a statistically significant difference (P=0.006). The prognosis of bladder cancer patients in the highTMB expression group was better than that in the low TMB expression group. In addition, TMB was correlated with gen-der (P=0.016) and tumor grade (P<0.001). The enrichment analysis of differentially expressed genes was significantly in-volved in the regulation of renin-angiotensin system, P13K-Akt signaling pathway, cytokine-cytokine receptor interac-tion, and Ras signaling pathway. In addition, differences in immune cell composition of CD8+ T cells, memory-activated
下载PDF