Identification Of Cell Cycle Relevant Genes Correlated With The Progression And Prognosis Of Human Bladder Cancer

Part ? Identification of cell cycle relevant genes highly correlated with progression and prognosis of human bladder urothelial tumorOBJECTIVE: To screen differentially expressed genes highly correlated with the development of bladder cancer(BCa)from the results of gene expression data by bioinformatics methods,and to provide potential non-invasive biomarkers and potential molecular drug targets for BCa.METHODS: The RNA sequencing data sets and corresponding clinical characteristics of BCa patients were downloaded from the GEO database website,and combined with the previous sequencing data of the research group,four data sets were processed using R language and taken in the intersection to screen difference expressed genes(DEGs).The differentially expressed genes(DEGs)were further identified by gene function enrichment,small molecule drug targets screening,protein-protein interaction(PPI)network construction,prognosis and staging correlation analysis,and finally we obtained several hub genes which are highly correlated with the progression of BCa.Immunohistochemical staining and quantitative real time PCR(q-PCR)was performed using BCa tissues to validate above results.RESULTS: After the intersection of the four microarray data sets,59 up-regulated genes and 40 down-regulated genes were obtained.The function and pathway enrichment indicated that these genes were highly correlated with cell cycle regulation.Based on the results of PPI network construction,prognostic correlation analysis of TCGA data and GSE13507 data,five DEGs highly related to disease-free survival(DFS)of BCa were obtained.Significant differences in BCa of these DEGs were further confirmed by tumor staging correlation analysis and genetic mutation analysis.The clinical tumor tissues collected from our biobank were used to verify the significant high transcriptional and translation expression of these genes in BCa.Conclusion: We finally obtained five genes with significant differential expression in BCa through bioinformatics methods,and these DEGs may regulate the occurrence and progression of tumor cells through cell cycle regulation.It can be inferred that these 5 genes are valuable in diagnosis,prediction,and providing candidate therapeutic targets for BCa patients of different stages.Part ? Effect and mechanism of proline-rich protein 11(PRR11)on the development of bladder cancerObjective: To verify the high expression of proline-rich 11(PRR11)in bladder tumors,and to detect the correlation between its expression and bladder tumor staging,grading and prognosis,and to explore its molecular mechanism in the development of bladder tumors.Methods: The results of sequencing microarray were visualized by bioinformatics method.The difference of PRR11 expression between bladder cancer tissues and normal bladder epithelium was compared.The expression of PRR11 and correlate tumor stage and clinical pathology information were tested by T test and analysis of variance.;Kaplan-Meier survival analysis to compare the correlation between PRR11 expression and clinical prognosis;transfection of bladder cancer cells with small interfering RNA and plasmid vector for in vitro functional assay;In vivo animal experiments were performed in a nude mouse tumor-bearing model;cell cycle changes were detected by flow cytometry.Results: The high expression of PRR11 in bladder cancer was confirmed by database results and internal tissue experiments,and the expression level was correlated with tumor T stage.The expression level of PRR11 was highly correlated with tumor prognosis,progression and survival;PRR11 can promote the proliferation,migration and colony formation abilities of bladder cancer cells.It can also promote the development of bladder cancer in vivo.The flow cytometry test confirmed that PRR11 affects the development of bladder cancer through cell cycle progression.Conclusion: PRR11 regulates the occurrence and development of bladder cancer by affecting cell cycle progression,and the expression level is related to the prognosis and survival of bladder cancer.