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基于生信分析构建泌尿系肿瘤铁死亡预后模型

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目的 通过生物信息学方法构建并验证泌尿系肿瘤铁死亡相关的预后模型。方法 分析TCGA中的膀胱癌(BLCA)和肾透明细胞癌(KIRC)数据集的RNA-seq及临床数据,建立预后模型,并使用ICGC和GEO数据进行验证。通过单变量Cox、LASSO-Cox和多变量Cox回归分析确定铁死亡相关预后基因。利用共表达和蛋白-蛋白互作网络分析基因间的关系,以及通过免疫浸润分析探讨基因与免疫微环境的关联。对BLCA和KIRC预后模型高低风险组的差异表达基因进行功能富集分析,探讨铁死亡相关基因调控这两种癌症预后的潜在机制。结果 在BLCA和KIRC中鉴定出与预后显著相关的铁死亡基因,包括 BLCA 的 EGR1、ZEB1、P4HB、WWTR1、JUN、CDO1、SCD、SREBF1、CAV1、GALNT14 等;KIRC 的 ASMTL-AS1、CHAC1、MT1G、RRM2、TIMP1、DPEP1、GLRX5、NDRG1等。此外,筛选出与两种癌症预后相关的铁死亡相关miRNA。基于这些基因和miRNA构建的风险模型预测了 TCGA-BLCA和KIRC患者的预后,其中低危组的总生存期显著高于高危组(P<0。05),模型的风险比范围为2。54(95%CI:1。73~3。74)至4。74(95%CI:3。47~6。47),AUC均在0。60以上。共表达分析和蛋白-蛋白互作网络显示BLAC中JUN与EGR1表达水平相关性高,SCD与SREBF1之间也存在相关性。免疫浸润相关性分析显示BLCA中EGR1、CAV1、JUN基因表达与免疫评分呈正相关,SREBF1与免疫评分呈负相关。结论 基于铁死亡相关基因的预后模型在预测BLCA和KIRC患者预后方面表现出良好的性能,可为靶向铁死亡评估BLCA和KIRC患者预后提供参考。
A ferroptosis prognosis model constructed for urological tumors based on bioinformatics analysis
Objective To construct and validate a prognosis model related to ferroptosis in urinary tract tumors u-sing bioinformatics methods.Methods RNA-seq and clinical data from TCGA's BLCA and KIRC datasets were analyzed to establish the prognostic model,and then were validated using ICGC and GEO data.Prognostic genes associated with ferroptosis were identified through univariate Cox,LASSO-Cox,and multivariate Cox regression an-alyses.Co-expression and protein-protein interaction(PPI)network analyses determined the relationships among these genes.Immune infiltration analysis explored the association between ferroptosis-related prognostic genes and the immune microenvironment.Functional enrichment analysis of differentially expressed genes between high and low-risk groups in BLCA and KIRC prognostic models was conducted to investigate potential mechanisms by which ferroptosis-related genes regulate BLCA and KIRC prognosis.Results Significant prognostic gene signatures asso-ciated with ferroptosis were identified in BLCA and KIRC.For BLCA,the genes EGR1,ZEB1,P4HB,WWTR1,JUN,CDO1,SCD,SREBF1,CAV1,and GALNT14 were significant.For KIRC,the genes ASMTL-AS1,CHAC1,MT1G,RRM2,TIMP1,DPEP1,GLRX5,and NDRG1 were significant.Ferroptosis-related miRNAs linked to the prognosis of both cancers were also identified.The constructed risk models based on these genes and miRNAs pre-dicted patient prognosis in TCGA-BLCA and KIRC,with low-risk groups showing significantly higher overall surviv-al(P<0.05).The hazard ratios for these models ranged from 2.54(95%CI:1.73-3.74)to 4.74(95%CI:3.47-6.47),with AUC values above 0.60.Co-expression analysis and PPI networks revealed high correlation levels between JUN and EGR1 in BLAC and between SCD and SREBF1.Immune infiltration analysis indicated positive correlations between EGR1,CAV1,JUN,and immune scores,while SREBF1 showed a negative correla-tion.Conclusion The prognosis model based on ferroptosis-related genes effectively predicts patient outcomes in BLCA and KIRC.This model can serve as a reference for targeting ferroptosis to assess the prognosis of BLCA and KIRC patients.

bladder urothelial carcinomarenal clear cell carcinomairon deathprognostic modelmiRNAsim-mune infiltration

沈忠杰、张俊勇、葛成国

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重庆医科大学附属第二医院泌尿外科,重庆 400010

膀胱尿路上皮癌 肾透明细胞癌 铁死亡 预后模型 miRNAs 免疫浸润

2024

安徽医科大学学报
安徽医科大学

安徽医科大学学报

CSTPCD北大核心
影响因子:1.095
ISSN:1000-1492
年,卷(期):2024.59(11)