PPARGC1A通过影响肿瘤微环境中免疫成分改善肾透明细胞癌的预后  

The role of PPARGC1A in improving the prognosis of renal clear cell carcinoma by affecting the immune components in the microenvironment of tumors

作　　者：储昭阳 朱向明[2] 江峰[2] 刘表虎[2] 李国杰[2] 龚儒杰[2] 马平川 徐凯慧 Chu Zhaoyang;Zhu Xiangming;Jiang Feng;Liu Biaohu;Li Guojie;Gong Rujie;Ma Pingchuan;Xu Kaihui(Graduate School,Wannan Medical College,Wuhu 241000,Anhui,China;Department of Ultrasonic Medicine,Yijishan Hospital of Wannan Medical College,Wuhu 241001,Anhui,China;Department of Ultrasonic Medicine,Taizhou Huangyan Maternal and Child Health Care Hospital,Taizhou 318020,Zhejiang,China)

机构地区：[1]皖南医学院研究生院,安徽芜湖241000 [2]皖南医学院弋矶山医院超声医学科,安徽芜湖241000 [3]浙江省台州市黄岩区妇幼保健院超声医学科,浙江台州318020

出　　处：《右江民族医学院学报》2020年第6期716-722,共7页Journal of Youjiang Medical University for Nationalities

基　　金：安徽省中央指导地方科技发展专项项目(017070802D152);皖南医学院重点研究项目培育基金(WK2017ZF01)。

摘　　要：目的通过分析肿瘤微环境(TME),确定与肾透明细胞癌(KIRC)关键基因相关的肿瘤浸润免疫细胞(TICs)的组成,揭示关键基因的独立预后价值。方法应用CIBERSORT和ESTIMATE计算方法,从癌症基因组图谱(TCGA)数据库中计算了611例KIRC患者免疫和基质成分的数量和TICs的比例。通过对差异表达基因(DEGs)进行了分析并进行Cox回归分析和构建蛋白质-蛋白质相互作用网络(PPI)。然后,通过单因素Cox与PPI的交集分析,确定过氧化物酶体增殖物激活受体γ共激活因子-1A(PPARGC1A)为预后因子。进一步对PPARGC1A的表达进行差异分析、生存分析、临床相关性分析、基因集富集分析(GSEA)、TICs组成比例及相关性分析。结果PPARGC1A的表达与临床病理特征(临床分期、远处转移)呈负相关,与KIRC患者的生存呈正相关。GSEA显示,高表达PPARGC1A组的基因主要富集于代谢途径和免疫相关活性。对TICs比例的CIBERSORT分析表明,幼稚B细胞、巨噬细胞M2与PPARGC1A表达呈正相关,但调节性T细胞(Treg)和T细胞滤泡辅助因子(Tfh)与PPARGC1A表达呈负相关,提示PPARGC1A可能负责调控TME的免疫成分。结论PPARGC1A的表达水平可能有助于改善KIRC患者的预后,特别可能通过影响TME的免疫成分发挥作用,同时也揭示了PPARGC1A作为免疫治疗发展的潜在靶点和生物标志物。Objective To determine the composition of tumor-infiltrating immune cells(TICs)related to key genes of renal clear cell carcinoma(KIRC)by analyzing the tumor microenvironment(TME),so as to reveal the independent prognostic value of key genes.Methods The CIBERSORT and ESTIMATE calculations were used to calculate the number of immune and matrix components and the proportion of TICs in 611 KIRC patients,of which the data was from The Cancer Genome Atlas(TCGA)database.By analyzing the differentially expressed genes(DEGs)and performing Cox regression analysis,the protein-protein interaction(PPI)network was constructed.Then,through the intersection analysis of single factor Cox and PPI,it was determined that peroxisome proliferator activated receptor gamma coactivator-1A(PPARGC1A)was a prognostic factor.Furthermore,we conducted differential analysis,survival analysis,clinical correlation analysis,gene set enrichment analysis(GSEA),TICs composition proportion and correlation analysis on the expression of PPARGC1A.Results The expression of PPARGC1A was negatively correlated with clinicopathological characteristics(clinical staging,distant metastasis),and positively correlated with the survival of KIRC patients.GSEA showed that the genes of the high PPARGC1A expression group were mainly enriched in metabolic pathways and immune-related activity.CIBERSORT analysis of the TICs proportion showed that naive B cells,macrophages M2 were positively correlated with the expression of PPARGC1A,but regulatory T cells(Treg)and T cell follicular cofactor(Tfh)were negatively correlated with the expression of PPARGC1,suggesting that PPARGC1A may be responsible for regulating the immune components of TME.Conclusion The expression of PPARGC1A may help improve the prognosis of KIRC patients,especially by affecting the immune components of TME.It also reveals PPARGC1A as a potential target and biomarker for the development of immunotherapy.

关 键 词：PPARGC1A 肿瘤微环境 ESTIMATE CIBERSORT 肿瘤浸润免疫细胞 肾透明细胞癌 

分 类 号：R737.11[医药卫生—肿瘤] R730.43[医药卫生—临床医学]