Preliminary Experimental Validation Of PMEPA1 Gene In Prostate Cancer Based On Bioinformatics Mining

Objective:Through immunohistochemical staining,the role of PMEPA1 genes discovered by bioinformatics in the occurrence and development of prostate cancer was explored,so as to provide new ideas for the diagnosis,treatment and prevention of prostate cancer.Methods:(1)An online Database was searched on the GEO dataset,and four datasets(GSE104935,GSE120005,GSE78201 and GSE21887)were included for further analysis.Differentially expressed genes(DEGs)were screened out using DAVID database was used for GO function analysis and KEGG pathway enrichment analysis,and P < 0.05 was considered statistically significant;(2)Using STRING database to construct a protein-protein interaction(PPI)network,importing the obtained source files into Cytoscape software(Cytoscape＿v3.6.1)for visual analysis of PPI network and screening of key Genes;(3)to verify the key genes,begin from Oncomine database to download protein expression and Survival data,get the key genes expressed in prostate cancer cases,and then USES the GEPIA database analysis key genes and PCA disease-free surial in patients with(Diseases Free Survival,DFS)and Overall Survival(OS),the relationship between the COX regression analysis using relevant data,to determine the final target genes;(4)In order to preliminarily verify the gene mined by bioinformatics method and software analysis(PMEPA1),cancer and paracancerous histomathological white film of 60 patients who underwent PCA radical surgery in our hospital from August 2018 to October 2020 were collected,and the results of bioinformatics analysis were detected by immunohistochemical staining.Results:(1)1151,828,894 and 2293 up-regulated genes were found in GSE104935,GSE120005,GSE78201 and GSE21887,and 1113,814,960 and 2027down-regulated genes were found in GSE104935,GSE120005,GSE78201 and GSE21887.There are 15 raised gene and 27 overlap down-regulated genes,the GO to function analysis and KEGG pathway enrichment analysis,found that overlap have focused on the essence of extranuclear omentum and nuclear weeks,these genes mainly involves phospholipid transfer protein activity,the structure of the protein domains and specific binding of long chain fatty acyl COA biosynthesis;(2)The interaction between proteins was studied and integrated by STRING,and the related data was further analyzed by Cytoscape,and 11 key genes were found,including 4 up-regulated genes(ELOVL6,ABCA1,FOXO3,TNRC6b)and 7down-regulated genes(ALDH1A3,OSBPL8,ACSL3,SLC45A3,KLK2,FKBP5,PMEPA1);(3)The relative expression of these 11 key genes in patients with low-risk prostate cancer and high-risk prostate cancer was analyzed,and it was found that ALDH1A3(P =0.038),OSBPL8(P =0.028),PMEPA1(P =0.039),KLK2(P =0.033),SLC45A3(P =0.012)and TNRC6b(P =0.036)had statistical significance.FKBP5(P=0.312),ABCA1(P =0.861),FOXO3(P =0.277),ACSL3(P =0.233)and ELOVL6(P=0.127)had no statistical significance.In addition,through the online analysis of GEPIA database,only PMEPA1 of the 6 genes was found to be related to the DFS of PCA(P =0.017),and all of them were unrelated to OS,because KLK2 was under-expressed in ONCOLNC.Therefore,Cox regression analysis of the remaining 5genes(ALDH1A3,OSBPL8,PMEPA1,SLC45A3 and TNRC6b)showed that OSBPL8 and SLC45A3 were correlated with survival rate;(4)Among the 60 pathological samples,the PMEPA1 gene was positive in 16 cases and negative in 44 cases.There were 53 positive cases and 7 negative cases in the paracancerous tissues.The expression of PMEPA1 gene in the paracancerous tissues of PCA patients was significantly different from that in the paracancerous tissues(P < 0.05);(5)The differential expression of PMEPA1 gene in PCA was negatively correlated with PSA(P=0.013,r=-0.318),Gleason score(P=0.025,r=-0.29),T stage(P=0.019,r=-0.302),risk grouping(P=0.036,r=-0.271)and bone metastasis(P=0.044,r=-0.26).There was no significant correlation between patients’ age(P=0.789)and CRPC stage(P=0.292).Conclusion:(1)Through bioinformatics,we excavated the differences in the expression of three genes,PMEPA1,OSBPL8 and SLC45A3,in prostate cancer,and also proved that bioinformatics method could effectively obtain the information of disease-related pathogenic factors;(2)PMEPA1 gene expression was significantly lower than in the prostate cancer tissue adjacent to carcinoma,and risk of PSA,Gleason score,with the patient group,the pathological T stage,negatively correlated with bone metastases,illustrates the PMEPA1 gene in the occurrence and development of prostate cancer have the effect of tumor suppressor genes,makes PMEPA1 genes have a prostate cancer diagnosis,prognostic judgement,the potential targets for drug treatment.