N6-甲基腺苷相关lncRNAs是预测肾癌患者预后和免疫浸润的潜在生物标志物

N6-methylandenosine-related lncRNAs are potential biomarkers for predicting prognoses and immune infiltrates in patients with renal cell carcinoma

目的:N6-甲基腺苷(m^(6)A)修饰和长链非编码RNA(lncRNA)在肾癌(RCC)的预后价值和肿瘤微环境(TME中发挥重要作用。本文旨在说明m^(6)A、lncRNA和免疫细胞浸润对RCC的影响。方法:采用Pearson相关分析、单因素分析、最小绝对收缩和选择算子获得与m^(6)A相关的lncRNAs,并进行多因素Cox回归分析构建m^(6)A相关的lncRNA风险模型。KaplanMeier分析和功能富集分析用于分析风险模型。采用TME和免疫相关性差异分析阐明免疫细胞浸润与临床预后的相关性。结果:包含9个m^(6)A相关lncRNAs的预后签名的风险模型被确定为独立预后因子。总生存期(OS)较短的聚类2显示出与CD8T细胞和滤泡辅助T细胞的相关性。功能富集分析结果表明mTOR、VEGF和Notch信号通路是显著富集的通路。风险评分与浆细胞、CD4记忆T细胞、CD8 T细胞、调节性T细胞和滤泡辅助T细胞的浸润水平呈正相关。结论:该预后模型有助于预测RCC的预后。m^(6)A相关lncRNAs及其在TME中的免疫细胞浸润可能为RCC治疗提供新的靶点。

Objective:N6-methyladenosine(m^(6)A)modification and long non-coding RNA(lncRNA)play important roles in prognostic value and tumor microenvironment(TME)of renal cell carcinoma(RCC).This article aimed to illustrate influence of m^(6)A,lncRNA and immune cell infiltration on RCC.Methods:Pearson correlation analysis,univariate analysis,least absolute contraction and selection operator were used to obtain m^(6)A-related lncRNAs,and conducted multivariate Cox regression analysis to construct model of m^(6)A-related lncRNAs.Kaplan-Meier analysis and functional enrichment annotation were used to analyze the risk model.Analyzed differences in TME and immune correlation to clarify the infiltration of immune cells and their correlation with clinical prognosis.Results:Risk model comprising nine m^(6)A-related lncRNAs prognostic signature was identified as an independent predictor of prognoses.Cluster 2 with a short overall survival(OS)showed a correlation with CD8 T cells and follicular helper T cells.mTOR,VEGF and Notch signaling pathway were the most significantly enriched according to the gene set enrichment analysis.The risk score was positively correlated with infiltration levels of plasma cells,CD4 memory T cells,CD8 T cells,regulatory T cells and follicular helper T cells.Conclusion:Prognostic model can help in the prediction of RCC prognosis.m^(6)A-lncRNAs and their related immune cell infiltration in TME may provide novel therapeutic targets for RCC.