Identifying Stage-associated Hub Genes in Bladder Cancer Via Weighted Gene Co-expression Network and Robust Rank Aggregation Analyses

Background: Bladder cancer (BC) is among the most frequent cancers globally. Although substantial efforts have been put to understand its pathogenesis, its underlying molecular mechanisms have not been fully elucidated.

Methods: The robust rank aggregation approach was adopted to integrate 4 eligible bladder urothelial carcinoma microarray datasets from the Gene Expression Omnibus. Differentially expressed gene sets were identified between tumor samples and equivalent healthy samples. We constructed gene co-expression networks using weighted gene co-expression network to explore the alleged relationship between BC clinical characteristics and gene sets, as well as to identify hub genes. We also incorporated the weighted gene co-expression network and robust rank aggregation to screen differentially expressed genes.

Results: CDH11, COL6A3, EDNRA, and SERPINF1 were selected from the key module and validated. Based on the results, significant downregulation of the hub genes occurred during the early stages of BC. Moreover, receiver operating characteristics curves and Kaplan-Meier plots showed that the genes exhibited favorable diagnostic and prognostic value for BC. Based on gene set enrichment analysis for single hub gene, all the genes were closely linked to BC cell proliferation.

Conclusions: These results offer unique insight into the pathogenesis of BC and recognize CDH11, COL6A3, EDNRA, and SERPINF1 as potential biomarkers with diagnostic and prognostic roles in BC.