肾透明细胞癌的多位点转录后甲基化修饰模式和免疫特征综合分析

Comprehensive analysis of multisite post-transcriptional methylation modification patterns and immune characteristics in kidney renal clear cell

目的通过系统分析肾透明细胞癌(KIRC)中多位点甲基化修饰模式与免疫特征的关系,以及在KIRC发生发展中的潜在机制,评估其对患者预后及治疗效果。方法从TCGA数据库中下载了KIRC的基因表达数据,并收集了与m6 A、m1 A、m5 C等多位点甲基化修饰相关的84个基因。通过差异表达分析,筛选出在肿瘤组织中显著上调或下调的甲基化相关基因。基于这些差异基因,使用共识聚类方法将患者分为三个亚群(C1、C2、C3),并分析了各亚群之间的临床特征差异、免疫浸润状态和免疫检查点表达水平及TIDE评分。结果不同亚群的患者在免疫浸润和生存预后存在显著差异(P<0.05)。通过单因素和多因素回归分析及LASSO回归,构建了基于差异甲基化基因的预后风险模型,并将患者分为高风险组和低风险组。高风险组患者的生存率显著低于低风险组(P<0.05)。此外,对不同亚群和不同风险组患者对常用化疗药物敏感性的评比,发现某些甲基化修饰与药物敏感性之间存在显著相关性(P<0.05)。结论肾透明细胞癌中多位点甲基化修饰模式与免疫微环境和临床预后密切相关,构建的预后模型为KIRC预测患者生存和个体化治疗策略提供了新的理论依据。

Objective To assess the prognostic and therapeutic effects on patients by systematically analyzing the relationship between multisite methylation modification patterns and immune characteristics in kidney renal clear cell carcinoma(KIRC)and explore the potential mechanisms involved in KIRC progression.Methods The gene expression data of KIRC were downloaded from the TCGA database,and 84 genes associated with multi-site methylation modifications such as m6A,m1A,m5C were collected.Methylation-related genes that were significantly up-or down-regulated in tumor tissues were screened by differential expression analysis.Based on these differentially expressed genes,patients were classified into three subgroups(C1,C2,and C3)using a consensus clustering method,and differences in clinical features,immune infiltration status and immune checkpoint expression levels,and TIDE scores were analyzed among the subgroups.Results There were significant differences in immune infiltration and survival prognosis among different subgroups of patients(P<0.05).A prognostic risk model based on the differentially methylated genes was constructed by univariate and multivariate regression analyses and LASSO regression,and patients were divided into high-risk and low-risk groups.The survival rate of patients in the high-risk group was significantly lower than that in the low-risk group(P<0.05).In addition,the evaluation of the sensitivity of patients in different subgroups and different risk groups to commonly used chemotherapeutic drugs revealed a significant correlation between certain methylation modifications and drug sensitivity(P<0.05).Conclusion This study reveals a close association between multi-site methylation modification patterns in KIRC and the immune microenvironment and clinical prognosis and the constructed prognostic model provides a new theoretical basis for predicting patient survival and individualized treatment strategies in KIRC.