早期肾透明细胞癌免疫基因相关预后模型的建立

Establishment of an Immune Gene Related Prognostic Model for Early Clear Cell Renal Cell Carcinoma

目的明确免疫相关基因的表达与早期肾透明细胞癌预后之间的关系,建立早期肾透明细胞癌免疫相关基因的预后模型,并评估该模型与肿瘤浸润免疫细胞之间的关系.方法下载TCGA公共数据中早期肾透明细胞癌的RNAseq数据及相应的临床信息,收集2018年1月至3月于北京协和医院泌尿外科经病理确诊为早期肾透明细胞癌的肿瘤组织及癌旁正常组织27对,采用液相色谱-质谱定量检测组织中的免疫相关蛋白的表达水平.根据相应的阈值,同时存在RNA和蛋白水平差异性表达的基因视为差异分子,构建基于差异免疫分子的预后模型,并计算每个样本的风险得分,使用TIMER在线网站计算肿瘤浸润免疫细胞的分布,利用Spearman相关性分析,评估肿瘤免疫基因的风险得分与肿瘤浸润免疫细胞之间的关系.结果本研究共筛选出261例TCGA早期肾透明细胞癌患者的RNAseq数据及相应的临床预后信息,同时收集了27对组织样本.通过差异性分析,最终确定了ARG2、HRG等15个差异性表达分子.COX线性回归模型建立了由FCGR3A、ZAP70、C3、VAV1、ANGPTL4所构成的预后模型,且高风险组的预后显著差于低风险组,差异有统计学意义(P=0.0024).多因素分析提示,由该模型所确定的风险分层是患者的独立预后因素(HR=1.7,P=0.021).相关性分析提示,肿瘤的风险得分与树突状肿瘤浸润免疫细胞具有相关性,差异有统计学意义(P<0.01).结论由5个免疫基因所构成的早期肾透明细胞癌预后模型可以准确地预测患者的预后,且与肿瘤微环境中的树突状细胞具有相关性.

Objective This study aimed to investigate the relationship between the expression of immune related genes and the prognosis of early clear cell renal cell carcinoma,to establish a prognostic model based on immune related genes for early clear cell renal cell carcinoma,and to evaluate the relationship between the model and tumor infiltrating immune cells.Methods RNA sequencing data for early renal clear cell carcinoma from TCGA public database and the corresponding clinical information were downloaded.A total of 27 pairs of tumor tissues and adjacent normal tissues were collected from the Department of Urology,Peking Union Medical College Hospital,from January to March 2018,and a diagnosis of early clear cell renal cell carcinoma was pathologically confirmed.The expression levels of immune related proteins in tissues were detected by liquid chromatography-mass spectrometry.According to the corresponding threshold,genes with differential expression at both the RNA and protein levels were regarded as differential molecules.A prognostic model based on differential immune molecules was constructed,and the risk score of each sample was calculated.The distribution of tumor infiltrating immune cells was calculated with the‘TIMER’online website,and Spearman correlation analysis was used.The relationship between the risk score of tumor immune genes and tumor infiltrating immune cells was evaluated.Results A total of 261 TCGA patients with early clear cell renal cell carcinoma were screened for RNA sequencing data and corresponding clinical prognosis information,and 27 pairs of tissue samples were collected.Finally,15 differentially expressed molecules,such as ARG2 and HRG,were identified.A Cox linear regression model established a prognostic model composed of FCGR3A,ZAP70,C3,VAV1 and ANGPTL4.The prognosis of the high-risk group was significantly worse than that of the low-risk group(P=0.0024).Multivariate analysis showed that the risk stratification determined by the model was an independent prognostic factor(HR=1.7,P=0.021).Correlation analysis showed that the tumor risk score was correlated with tumor infiltrating dendritic immune cells(P<0.01).Conclusion A prognostic model of early clear cell renal cell carcinoma,composed of five immune molecules,was constructed.The model can accurately predict the prognosis of patients with clear cell renal cell carcinoma and correlates with dendritic cells in the tumor microenvironment.