摘要
Abstract
Objective To investigate the clinical application value of nerve guidance factor 4(NTN4)in clear cell renal cell carcinoma(ccRcc).Methods TCGA,UALCAN and HPA databases were used to compare the expression level of NTN4 messenger RNA(mRNA)in adjacent tissues and ccRcc tissues,and the expres-sion level of NTN4 protein in normal kidney tissues and ccRcc tissues.The surv_cutpoint()function of sur-vminer package was used to determine the best cut-off value of NTN4 expression level,and the patients were divided into NTN4 high expression group and NTN4 low expression group according to the best cut-off value.The relationship between NTN4 expression level and clinical characteristics of ccRcc patients and its effect on prognosis of ccRcc patients were analyzed.Receiver operating characteristic(ROC)curve was drawn to ana-lyze the diagnostic value of NTN4 in ccRcc patients.Kaplan-Meier survival curve and Log-Rank test were used to analyze the survival of NTN4 high expression group and NTN4 low expression group.Univariate and multi-variate Cox regression analysis were used to analyze the risk factors of ccRcc prognosis.NTN4 promoter methylation level(Beta value)was compared between ccRcc and normal kidney tissues.Gene set enrichment analysis(GSEA)was used to explore the potential mechanism of NTN4 in ccRcc tissues and construct a no-mogram prediction model,and Calibration curve was used to verify the model.Results A total of 72 adjacent tissues and 533 ccRcc tissues(including 72 paired tissues)were selected from TCGA database.The expression level of NTN4 mRNA in 533 ccRcc tissues was significantly lower than that in adjacent tissues(P<0.05).The expression level of NTN4 mRNA in 72 ccRcc tissues was significantly lower than that in adjacent non-cancerous tissues(P<0.05).The results of UALCAN database analysis showed that the expression level of NTN4 protein in ccRcc tissues was significantly lower than that in normal kidney tissues(P<0.05).There were 384 patients in the NTN4 high expression group and 149 patients in the NTN4 low expression group.There were significant differences in histological grade,pathological stage,tumor size,local invasion(T stage)and distant metastasis(M stage)between NTN4 low expression group and NTN4 high expression group(P<0.05).ROC curve analysis showed that the area under the curve of NTN4 for the diagnosis of ccRcc was 0.881(95%CI:0.847-0.916)The best cut-off value was 6.68,the sensitivity was 0.65,and the specificity was 0.94.Kaplan-Meier survival curve analysis showed that the prognosis of ccRcc patients in the NTN4 high expression group was better than that in the NTN4 low expression group(P<0.05).Univariate and multiva-riate Cox regression analysis showed that low expression of NTN4,age>60 years and M stage of M1 were independent risk factors for poor prognosis of ccRcc patients(P<0.05).Compared with normal kidney tis-sues,the Beta value of NTN4 was significantly increased in ccRcc tissues(P<0.05).The Calibration curve a-nalysis results of the nomogram prediction model showed that the C-index of the nomogram model was 0.728.GSEA results showed that NTN4-related genes were mainly enriched in RNA splicing,endocytosis,ubiquitin-mediated protein degradation,neurotrophic factor signaling pathway and other related pathway.Con-clusion The expression of NTN4 is decreased in ccRcc,and it may be used as a biomarker for predicting the prognosis of ccRcc patients.关键词
肾透明细胞癌/神经导向因子4/癌症基因组图谱/诊断/预后Key words
clear cell renal cell carcinoma/neural guidance factor 4/the cancer genome atlas/diagno-sis/prognosis分类
医药卫生
