Analysis Of Potential Molecular Markers And Their Prognostic Values In Renal Clear Cell Carcinoma By Bioinformatics Analysis

Objective:Renal cell carcinoma is the most common malignant tumor of the kidney.It accounts for about 90% of all malignant tumors of the kidney.In the world,renal cell carcinoma ranks sixth in male malignant tumors and ranks tenth among females.It accounts for 5% and 3% of all malignant tumors.Renal clear cell carcinoma is the most common pathological type of renal cell carcinoma,accounting for about 75%.Renal clear cell carcinoma is mainly treated with surgery.Most patients have distant metastasis at the time of diagnosis,and the prognosis is poor.Renal clear cell carcinoma is insensitive to chemotherapy and radiation therapy,and the effects of molecular targeted therapies and immunotherapy are currently not obvious and expensive.Therefore,to study the molecular mechanism of the occurrence and development of renal clear cell carcinoma,to find important molecular markers as potential targets for diagnosis,monitoring and treatment,is of great significance for the prevention,control and individualized treatment of renal clear cell carcinoma.In this study,bioinformatics analysis of renal clear cell carcinoma gene chip data was conducted to find differential genes and their biological functions related to the development of renal clear cell carcinoma.And to find out the core genes with iconic functions,clear signaling pathways with significant effects,provide a theoretical basis for the molecular mechanism research and prevention,monitoring and treatment of renal clear cell carcinoma.Methods:GSE36895 gene expression data was downloaded from the GEO database,including 29 renal clear cell carcinomas,24 mice implanted in situ with renal clear cell carcinoma,and 23 normal renal cortical tissues.The raw data was analyzed by R language to screen out differential genes.The differential genes were introduced into the DAVID database for GO functional analysis and KEGG pathway analysis to understand the biological functions of the differential genes themselves and the signaling pathways involved.Then,the differential gene was introduced into the STRING database to evaluate the correlation of the gene products,and a protein interaction network map was obtained.Download the relevant data obtained in the STRING database.The CYTOSCAPE software is used to screen the core genes with the iconic function.The MCODE plug-in is used to analyze the protein interaction network diagram,and then the KEGG pathway analysis of the genes in the module is performed.signal path.Finally,it was verified by the GEPIA database whether the expression levels of these core genes are significantly correlated with the pathological stage and survival prognosis of renal clear cell carcinoma.Results:After analysis,we obtained 1814 differentially significant expression genes,of which 643 were up-regulated and 1171 were down-regulated.GO functional analysis and KEGG pathway analysis revealed that up-regulated differential genes were mainly enriched in cell cycle,DNA replication,and p53 signaling pathways.The top 10 core genes were obtained by constructing a protein-protein interaction network as follows: CDK1,CDC20,CCNB1,CCNA2,PLK1,AURKB,BUB1 B,MAD2L1,CDCA8,KIF11,which are mainly involved in the cell cycle signaling pathway.Using the GEPIA database,all core genes were expressed more in clear cell renal cell carcinoma tissues than normal tissues.Except for the MAD2L1 gene,the expression levels of all core genes were significantly correlated with the pathological stage of clear cell renal cell carcinoma.High expression of AURKB,BUB1 B,CDC20,CDCA8,CDK1 and PLK1 showed shorter overall survival and disease-free survival,p values were <0.05,with significant statistical differences,and with the increased expression of these genes,overall the survival curves are gradually reduced and they are significantly associated with the prognosis of clear cell renal cell carcinoma.High expression of CCNA2 showed a short overall survival,but no significant difference in disease-free survival.High expression of CCNB1 and KIF11 showed shorter diseasefree survival,but there was no significant difference in overall survival.High expression of MAD2L1 showed no significant difference in overall survival and disease-free survival.Conclusions:1.The differentially expressed genes in clear cell renal cell carcinoma is mainly involved in the cell cycle process,including DNA replication,nuclear division,chromatid separation,G1/S phase conversion and other biological processes.2.Differences in signal pathways such as cell cycle,p53 signaling pathway,DNA replication,and central carbon metabolism of cancer may be involved in the occurrence and progression of clear cell renal cell carcinoma.3.CDK1,CDC20,CCNB1,CCNA2,PLK1,AURKB,BUB1 B,MAD2L1,CDCA8,KIF11 are the core genes with landmark functions.The core genes other than MAD2L1 are significantly associated with the pathological stage and survival prognosis of clear cell renal cell carcinoma.The above genes and participating pathways are closely related to the occurrence and progression of clear cell renal cell carcinoma,and can be used as potential targets for diagnosis and treatment.