基于数据库挖掘分析USH2A在结直肠腺癌中潜在的预后价值及其与肿瘤突变负荷和抗肿瘤免疫的相关性

Analysis of potential prognostic value and its correlation with tumor mutation burden and anti-tumor immunity of USH2A in colorectal adenocarcinoma patients based on database

目的利用TCGA和ICGC数据库,分析USH2A突变在结直肠腺癌患者中潜在的预后价值及其与肿瘤突变负荷(TMB)和抗肿瘤免疫的相关性。方法通过R语言软件筛选出TCGA和ICGC数据库中结直肠腺癌高频突变基因,分析其与TMB的相关性;使用Kaplan-Meier生存曲线分析高频突变基因的生存差异,利用Cox比例风险回归模型进一步分析结直肠腺癌患者临床特征、TMB、USH2A突变与预后的关系;利用GSEA软件对USH2A进行功能富集分析,探究与USH2A相关的信号通路;利用CIBERSORT法评估肿瘤样本中免疫细胞浸润的占比差异,并分析USH2A与肿瘤免疫细胞浸润的相关性。以P<0.05为差异具有统计学意义。结果本研究筛选出20个与TMB突变相关的基因;Kaplan-Meier生存分析证实,USH2A突变与结直肠腺癌患者的生存和预后有关,且突变组预后更差(P=0.0009);Cox回归分析显示,USH2A突变可作为影响结直肠腺癌的独立预后因素;GSEA富集分析显示朊病毒病、自然杀伤细胞介导的细胞毒作用途径、免疫球蛋白肠道免疫网络、自身免疫性甲状腺疾病、抗原提呈和处理途径在USH2A突变中出现富集;CIBERSORT结果表明,USH2A突变组中CD8^(+)T细胞、滤泡辅助性T细胞和激活NK细胞浸润比例更高;矩阵分析显示,CD8^(+)T细胞、滤泡辅助性T细胞和激活NK细胞之间呈正相关。结论USH2A突变可用于预测结直肠腺癌的预后,且与TMB和抗肿瘤免疫浸润相关,为进一步的治疗提供了潜在靶点。

Objective To explore the potential prognostic value of USH2A gene mutations,and its relationship between tumor mutation burden(TMB)and anti-tumor immunity of USH2A gene mutations in patients with colorectal adenocarcinoma by data mining through The Cancer Genome Atlas(TCGA)database and International Cancer Genome Consortium(ICGC)database.Methods R language software was used to obtain the intersection genes with high frequencies mutations,and to analyze the correlation between the intersection genes and TMB.The survival differences among the intersection genes were analyzed by Kaplan-Meier survival curve.Cox regression model was used to analyze the relationship among patient′s clinical characteristics,TMB,USH2A mutation for the survival of patients with colorectal adenocarcinoma.Gene Set Enrichment Analysis(GSEA)was used for gene enrichment analysis,to explore the signal pathways related to USH2A mutations gene in colorectal adenocarcinoma.The proportion of infiltrating immune cells in each tumor sample was obtained using CIBERSORT method,and to analyze the correlation between USH2A mutation gene and tumor infiltrating immune cells.In all comparisons,a P-value<0.05 was considered statistically significant.Results We screened twenty differential genes which were associated with TMB mutation.Kaplan-Meier survival analysis confirmed that USH2A mutation was related to the survival and prognosis of patients with colorectal adenocarcinoma,and associated with a worse prognosis(P=0.0009).Cox regression analysis showed that USH2A mutation could be as an independent prognostic factor for colorectal adenocarcinoma.GSEA enrichment analysis showed that some pathways were significantly enriched in the USH2A mutant group,including prion disease,natural killer cell mediate cytotoxic pathway,intestinal immune network for IgA production,autoimmune thyroid disease,antigen presentation and presentation.CIBERSORT results showed that the infiltration proportion of CD8^(+)T cells,follicular helper T cells and activated NK cells were higher in the USH2A mutation group.Matrix analysis revealed that there was a positive correlation among the CD8^(+)T cells,follicular helper T cells and activated NK cells.Conclusion USH2A mutation could be used to predict the prognosis of colorectal adenocarcinoma,and is related to TMB and anti-tumor immune infiltration,which provides a potential target for further treatment.