| Background Kidney cancer accounts for about 3% of adult malignant tumors,ranking third in the incidence of urinary system tumor.And clear cell renal cell carcinoma(cc RCC)accounting for about 80% of renal cancers is the most common pathological type.Patients usually have no obvious symptoms and signs early in the disease,so often lead to delay and progression.About 70 percent of kidney cancers are local or locally advanced at the time of initial diagnosis and can be treated with surgery.However,the patients who have metastatic kidney cancer metastatic renal cancer prognosis is poor due to not sensitive to traditional chemoradiotherapy.Oxidative Stress(OS)refers to a state of imbalance between oxidation and antioxidant functions in human body,which can lead to neutrophil infiltration and increase of protease secretion,during which a large number of Oxidative intermediates,reactive oxygen species,are produced.ROS(reactive oxygen species)play an importamt part in tumor genesis and progression.There is increasing proof that oxidative stress-related genes can be used as biomarkers for predicting malignant tumor progression and patient prognosis.However,the relationship between oxidative stress-related genes and renal clear cell carcinoma is unclear.ObjectiveTo explore the potential prognostic value of oxidative stress-related genes and construct a prognostic model based on oxidative stress genes in renal clear cell carcinoma.MethodsThe transcriptome data and clinical information of patients with renal clear cell carcinoma were downloaded from The cancer genome atlas(TCGA)database,and the differentially expressed genes related to oxidative stress were screened by Lasso cox regression analysis.The risk score was used to construct the prognostic prediction model of renal clear cell carcinoma,and the ROC curve was used to evaluate the performance of the model.Gene Set Enrichment Analysis(GSEA),immune cell infiltration components were performed in different risk groups to evaluate the correlation between risk score and immunotherapy.This model provides theoretical support for predicting the prognosis of patients with renal clear cell carcinoma and reveals potential therapeutic targets.ResultFrom 402 genes related to oxidative stress,10 genes(AGER,CRP,EDN1,EME2,HP,IFNG,MMP9,NR3C2,PPARGC1 A,VWF)were selected to participate in the model construction.According to the risk score,the samples were divided into high and low risk groups.K-M survival curve and ROC curve confirmed that the prognosis between the two groups was difference(P value <0.001),and the area under the curve was >0.7.Multivariate COX regression further confirmed that risk score was an independent prognostic predictor of Overall Survival(OS).The results of GSEA enrichment analysis showed that genes was enriched in the immunologic function pathway.Cellular immunity analysis showed that higher risk group was mainly infiltrated by follicular helper T cells,regulatory T cells(Tregs),and M0 macrophage,while the low-risk group was mainly infiltrated by memory resting CD4+T cells,M1 macrophages,resting dendritic cells and non-activated mast cells.And in immunotherapy,the high-risk group is more likely to occur tumor immune escape.The expression of immune checkpoint was different in the two groups.ConclusionIn this study,we established a prognostic model of renal clear cell carcinoma based on10 oxidative stress-related genes,and confirmed the riskscore can be used as an independent predictor signature of patients’ prognosis with renal clear cell carcinoma.The model provides a reference for the treatment and prognosis of patients with renal clear cell carcinoma,and it is speculated that patients with high risk score are more likely to have tumor immune escape.However,the underlying mechanism is still lacking and needs further exploration. |
