Study On The Role And Mechanism Of DLGAP5 As A Biomarker For Diagnosis And Prognosis Of Bladder Cancer

Background and Aim:Bladder cancer is one of the most common malignant tumors of the urinary system and the tenth most common cancer in the world.According to statistics,about549393 new confirmed cases and 199922 cases died of bladder cancer in 2018,which brings a huge burden to patients and society.One of the important characteristics of bladder cancer is its easy recurrenceand metastasis.However,the clinical reexamination of bladder cancer patients with bladder preservation mainly depends on invasive cystoscopy.Based on the fact that the biological diagnosis and prognostic markers of bladder cancer have not been widely used in clinic,we urgently need to find new biological markers for the diagnosis and prognosis of bladder cancer,which is not only beneficial to the early diagnosis of bladder cancer,and it is convenient for the reexamination of postoperative bladder cancer patients who retain the bladder.According to the literature,it has been reported that Disks large-associated protein 5(DLGAP5)is a potential regulator of cancer cell carcinogenesis and a mitotic regulatory factor,which mainly participates in the occurrenceand development of tumor in the cell cycle,promotes microtubule polymerization,bipolar spindle formation and stable microtubule.Eissa and his colleagues found that DLGAP5 can be detected in urine and can predict bladder cancer related to schistosomiasis.The mechanism of DLGAP5 involved in biological behaviors such as the occurrenceand development of bladder cancer is not clear.Bioinformatics analysis has been widely used to study various cancers and other diseases,to study the mechanism of occurrenceand development,biological functions and biomarkers of diseases,so as to improve diagnosis and treatment.In 2011,Salmena L et al proposed the competitive endogenous RNA(ceRNA)hypothesis,which reveals the potential regulatory relationship between RNA molecules in the occurrenceand development of the disease.Lnc RNA has a mi RNA binding site and can be used as an endogenous RNA,which can competitively bind to targeted mi RNA,thus reducing the gene inhibition of mi RNA.The purpose of this study is to explore the diagnostic and prognostic efficacy,biological behavior and potential RNA regulatory pathway of DLGAP5 in bladder cancer through bioinformatics analysis.This gene may be a potential therapeutic target for bladder cancer.Methods:The transcriptome data and clinical related data of bladder cancer were obtained from the cancer genome atlas(TCGA)database and gene expression omnibus(GEO)database.The differential expression of DLGAP5 mRNA in bladder cancer tissue was analyzed by R software,and the differential expression analysis was verified by bladder cancer gene chip in GEO database.The diagnostic efficacy of DLGAP5 in bladder cancer was explored by receiver operating characteristic curve analysis(ROC).Kaplan-Meier survival curve analysis and univariate and multivariate cox regression analysis were constructed to explore the prognostic analysis of DLGAP5 in bladder cancer.Progno Scan database was used to verify the prognostic analysis of DLGAP5 in bladder cancer patients.To further explore the immune cell infiltration analysis of DLGAP5 in bladder cancer by R software.Predicting the top 10 proteins of DLGAP5 through STRING online database to construct protein-protein interaction network,and analyze the gene ontology(GO)and the Kyoto encyclopedia of genes and genomes(KEGG)enrichment.The targeted mi RNAs of DLGAP5 and its corresponding targeted lnc RNAs and targeted circ RNAs were predicted by Star Base database,and the ceRNA network of bladder cancer was constructed by Cytoscape software.Results:The expression of DLGAP5 mRNA in bladder cancer tissues was significantly higher than normal bladder tissues and paracancerous tissues,and the differential expression analysis of GSE3167,GSE7476 and GSE65635 in bladder cancer tissues verified by GEO microarray showed that the expression level of DLGAP5 in bladder cancer tissues was higher than normal bladder tissues.However,the high expression of DLGAP5 was associated with histological grade(P<0.001),lymphaticvascular invasion(P=0.027),overall survival event(OS)(P=0.01),disease-specific survival event(DSS)(P=0.06)and progression-free interval event(DFI)(P=0.007).The univariate and multivariate Cox analysis showed that DLGAP5 could be used as an independent prognostic factor of bladder cancer;The ROC curve analysis showed that DLGAP5 had high diagnostic efficacy in patients with bladder cancer,and the area of ROC curve was 0.913.The results of immune infiltration analysis showed that the expression of DLGAP5 was positively correlated with the infiltration of Th1 and Th2 cells,and negatively correlated with NK CD56 bright and p DC cells(P < 0.001).The results of enrichment analysis showed that the enrichment of KEGG pathway of DLGAP5 was mainly concentrated in cell cycle,p53 signal pathway,cell senescenceand viral carcinogenic signal pathway.Conclusions:The expression of DLGAP5 mRNA in bladder cancer tissues is significantly higher than that in normal tissues or adjacent tissues,which is related to the poor prognosis of OS,PFI and DSS in patients with bladder cancer.DLGAP5 gene can be used as an independent prognostic and diagnostic biomarker of bladder cancer.The gene is mainly involved in the biological function of nuclear division and enriched in cell cycle and p53 signal pathway.Its expression level is positively correlated with Th1 and Th2 cells,and negatively correlated with NK CD56 bright and p DC cells.NEAT1/MALAT1/XIST/PKD--Hsa-mir-101-3p--DLGAP5 is a potential RNA regulatory pathway in bladder cancer,which may regulate the occurrenceand development,invasion and metastasis,cell proliferation and chemosensitivity of bladder cancer,and is a potential therapeutic target for bladder cancer.