肾透明细胞癌铁死亡相关亚型的分析与预后列线图的建立

Analysis of ferroptosis-related subtypes and establishment of prognostic nomogram in clear cell renal cell carcinoma

目的利用生物信息学方法对肾透明细胞癌(ccRCC)患者进行铁死亡相关亚型分析,筛选与预后显著相关的铁死亡相关基因,并建立列线图。方法在癌症基因组图谱(TCGA)数据库中下载具有临床数据的526例ccRCC和72例癌旁正常组织的转录组数据及临床数据,数据提取时间为建库起至2020年11月5日。采用围绕中心点划分(PAM)算法确定亚型数量。采用基因本体数据库(CO)功能富集分析和京都基因与基因组百科全书(KEGG)功能富集分析探索潜在功能与通路。采用单因素Cox、Kaplan-Meier生存曲线分析及最小绝对值收敛和选择算子(Lasso)回归分析和多因素Cox分析筛选ccRCC铁死亡相关基因,并建立列线图。结果共确定了4种ccRCC铁死亡相关亚型,分别为clusterl~4。富集分析发现亚型特征基因与细胞免疫、肿瘤微环境密切相关。筛选得到了10个ccRCC铁死亡相关基因(HMOX1、MT1G、CHAC1、LURAP1L、CXCL2、RRM2、TRIB3、DUSP1、GABARAPL1、ALOX12B)。建立了包含年龄、M分期、病理分期、组织分级和风险评分的列线图,列线图的1、3、5年的受试者工作特征(ROC)曲线下面积分别为0.858、0.809.0.774。结论确定4种ccRCC铁死亡相关亚型,亚型分型与患者临床预后相关。研究所建立的列线图对ccRCC患者预后有较好的预测能力,模型的ccRCC铁死亡相关基因可作为研究ccRCC发病机制和靶向治疗的靶点。

Objective To analyze ferroptosis-associated subtypes in patients with clear cell renal cell carcinoma(ccRCC),choose ferroptosis-associated genes significantly related to prognosis,and to establish a prognostic nomogram with bioinformatics methods.Methods Transcriptome data and clinical data of 526 ccRCC patients and 72 paracancer normal tissues with clinical data were downloaded from the Cancer Genome Atlas(TCGA)database,and the data were extracted from the database until November 5,2020.The number of subtypes was determined by PAM algorithm.Gene Ontology Database(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KECG)functional enrichment analysis explore potential functions and pathways.Single-factor Cox analysis,Kaplan-Meier survival curve analysis,minimum absolute convergence and selection operator(Lasso)regression analysis and multi-factor Cox analysis screened the genes related to iron death in ccRCC,and established a column diagram.Results Four ferroptosis-associated subtypes of ccRCC were identified and their clinical features and survival characteristics were analyzed.Enrichment analysis showed that subtype signature genes were closely related to cellular immunity and tumor microenvironment.Ten ccRCC ferroptosis-associated genes(HMOX1,MT1G,CHAC1,LURAP1L,CXCL2,RRM2,TRIB3,DUSP1,GABARAPL1,ALOX12B)were choosed.A nomogram containing age,M staging,pathological staging,tissue grading and risk score was established,and the areas under the ROC curve of the nomogram in 1 year,3 and 5 years were 0.858,0.809 and 0.774,respectively.Conclusions Four ferroptosis-associated subtypes of ccRCC are identified,and the subtypes are associated with clinical prognosis.The nomogram has good predictive ability for the prognosis of patients with ccRCC,and the ferroptosis-associated genes of ccRCC in the model can be used as targets for studying the pathogenesis and targeted therapy of ccRCC.