Bioinformatics Analyses Of Biomarkers Associated With Progression And Prognosis In Bladder Cancer

Background As one of the most common genitourinary malignancies,bladder cancer has a high rate of recurrence and progression.In addition,even after systemic therapy,the prognosis for patients with bladder cancer is still poor,especially for patients with muscle-invasive bladder cancer.Identifying biomarkers for bladder cancer and exploring the underlying disease mechanisms are still the emphases of bladder cancer research.Objective To identify more effective biomarkers for bladder cancer and explore the underlying disease mechanisms by a series of bioinformatics methods.Methods Weighted gene co-expression network analysis and protein–protein interaction network analysis as well as survival analysis were conducted to identify hub genes correlated with the bladder cancer progression and prognosis.These potential biomarkers were then validated and analyzed by bioinformatics methods.In addition,the relationships between COL5A1 and clinical characteristics were explored,as well as the mechanisms of how COL5A1 contributed to bladder cancer progression and prognosis.Results Six potential biomarkers(COL3A1,FN1,COL5A1,FBN1,COL6A1 and THBS2)correlated with the progression and prognosis of bladder cancer were identified by co-expression network analysis and protein–protein interaction network analysis as well as survival analysis.These potential biomarkers were then validated and analyzed,the results indicated that these 6 potential biomarkers were closely correlated with bladder cancer progression and could distinguish non–muscle-invasive bladder cancer and muscle-invasive bladder cancer.COL5A1 was further validated to be correlated with the progression and poor prognosis of bladder cancer.Furthermore,COL5A1 was validated correlated with some clinical characteristics of bladder cancer,including stage,grade,T and N.Functional and pathway enrichment analysis indicated that GO terms and pathways associated with the ECM and immunity were correlated with the progression and poor prognosis of bladder cancer patient with COL5A1 higher expression.In addition,several micro RNAs were also identified by bioinformatics methods,which might contribute to the progression and poor prognosis of bladder cancer patient with COL5A1 higher expression.Conclusions This study not only identified several biomarkers closely correlated with bladder cancer progression and prognosis,but also explored the underlying disease mechanisms.As novel findings,these may help to understand the mechanisms of bladder cancer and provide clues for the later researches.