| Objective: To explore the key genes,molecular biomarkers and the potential therapeutic drugs of clear cell renal cell carcinoma(ccRCC).Methods: The GSE68417 was downloaded from the GEO database,and the differential expression genes ware analyzed by GEO2 R,an online analysis tool.The mRNA expression data and clinical data of ccRCC were downloaded from the TCGA database,and edgeR package of R software was used to analyze the differentially expressed genes.The intersection of differentially expressed genes from two datasets were got by Veen calculation.And the protein interaction network and key genes were obtained by using the STRING database and the MCODE plug-in of Cytoscape 3.7.2 software.After analyzing the correlation between key genes and survival,the oncomine database and the human atlas database were used to verify the expression differences of key genes related to prognosis in mRNA and protein levels.Finally,CMap database was used to explore potential small molecular therapeutic drugs for ccRCC.Results: A total of 498 DEGs were obtained,of which 369 were up-regulated and 129 down regulated.The differentially expressed genes are mainly enriched in cytokine receptor interaction,signal pathway,drug metabolism,cell adhesion molecules and glycolysis.In addition,eight key genes related to ccRCC were screened,including EHF,ATP6V1C2,GPD1 L,DAO,FCER1 G,C1QA,FCGR2 B and SLC30A2,which were significantly different and correlated with prognosis.At last,Levobunolol,Benzbromarone and Indoprofen are three potential small molecular drugs for ccRCC.Conclusion: In conclusion,EHF,ATP6V1C2,GPD1 L,DAO,FCER1 G,C1QA,FCGR2 B and SLC30A2 may be the driving genes of ccRCC.More importantly,they may be new biomarkers to diagnose and guide ccRCC treatment strategies.In addition,Levobunolol,Benzbromarone and Indoprofen may be potential drugs for the treatment of ccRCC.Objective: The purpose of this study is to use TCGA database to evaluate the expression level of key genes representing EHF in cc RCC,analyze its role in the occurrence and development of cc RCC and the effect of low expression of EHF on the prognosis of patients with cc RCC,and further verify the results of the first part of the study.Methods: Based on the results of the first part of the study.EHF,one of the key genes,was selected to evaluate the expression difference between renal clear cell carcinoma and normal tissues.Oncomine database and the human database were used Finally,the expression level of EHF and its protein was detected by real-time quantitative polymerase chain reaction(q RT-PCR)and Western blot(Wb).Pearson rank sum test was used to analyze the correlation between EHF and other key genes.ANOVA and logistic regression were used to analyze the relationship between EHF and clinicopathological characteristics.Kaplan Meier method and Cox proportional hazard model were used to evaluate the relationship between EHF and overall survival rate.Results: Totally 70 para-cancerous and 541 cc RCC tissues were obtained from TCGA database.The results showed that the expression of EHF in cc RCC(60.62 ± 22.07)was lower than that in adjacent renal tissues(257.40 ± 66.81)(P < 0.001),the expression of EHF in cc RCC was 0.674(P < 0.001),the expression of EHF in OS and DFS was(P = 0.027)and(P = 0.497),respectively.The results of q RT-PCR showed that the expression of cc RCC was lower than that of normal tissues(P = 0.045).Wb suggested that the protein expression of cc RCC was significantly lower than that of normal tissues.The EHF gene was positively correlated with other key genes obtained in the first part by Pearson test,and only five of them were correlated: ATP6V1C2(r = 0.587,P < 0.001),GPD1L(r = 0.387,P < 0.001)and SLC30A2(r = 0.232,P < 0.001)were positively correlated with EHF,while DAOA(r =-0.265,P < 0.001)and FCGR2B(r =-0.238,P < 0.001)were negatively correlated with EHF.The expression of EHF decreased with T stage(P = 0.02),lymph node status(P < 0.001),clinical stage(P < 0.001),and grade(P < 0.001).Kaplan Meier survival analysis showed that the prognosis of lower expression level of EHF was worse than that of higher expression level(P < 0.001).Single variable and multivariate Cox analysis showed that EHF was an independent prognostic factor of cc RCC.Conclusion: The results showed that the expression of EHF in ccRCC decreased significantly.Among the selected key genes,ATP6V1C2,GPD1 L and SLC30A2 were positively correlated with EHF,while DAOA and FCGR2 B were negatively correlated with EHF.The expression of EHF was significantly correlated with T stage,lymph node status and clinical stage.EHF may be a potential prognostic marker of cc RCC. |
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