Identification of hub genes associated with bladder cancer using bioinformatic analyses

Bladder cancer (BLCA) is the ninth most common cancer worldwide, with high mortality and recurrence rates. Studies have increasingly reported that molecular diagnosis contributes to the early diagnosis and prognostic assessment of diseases. Thus, this study aims to find new biomarkers for the diagnosis and prognosis of BLCA.

The microarray datasets GSE147983 and The Cancer Genome Atlas (TCGA)-BLCA mRNA were obtained from the Gene Expression Omnibus (GEO) and TCGA. Differentially expressed genes (DEGs) were screened using the R "Limma" package. The "ClusterProfiler" package was used to conduct Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DEGs. A DEG protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape. The functional module was reanalyzed using Cytoscape's Molecular Complex Detection ("MCODE") plugin, and key genes related to BLCA were identified via the "cytoHubba" plugin. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and the Tumor Immune Estimation Resource (TIMER) were used to verify the correlation between hub gene expression and immunity. A survival analysis of hub genes was performed using the Kaplan-Meier Plotter online tool.

A total of 355 DEGs were screened out, including 236 upregulated and 119 downregulated DEGs. Some of the GO terms and pathways, such as chromosome separation, cell cycle, and cell senescence, were found to be significantly enriched in the DEGs. The key genes were kinesin family member 11 (KIF11), DLG associated protein 5 (DLGAP5), non-SMC condensin I complex subunit G (NCAPG), cell division cycle 20 (CDC20), cyclin B2 (CCNB2), BUB1 mitotic checkpoint serine (BUB1B), TPX2 microtubule nucleation factor (TPX2), NUF2 component of NDC80 kinetochore complex (NUF2), kinesin family member 2C (KIF2C), and cyclin B1 (CCNB1). Nine of them were immune-related, including KIF11, DLGAP5, NCAPG, CDC20, CCNB2, BUB1B, NUF2, KIF2C, and CCNB1. Survival analysis showed that the overexpression of BUB1B, CCNB1, CDC20, and DLGAP5 significantly reduced overall survival (OS) in patients with BLCA.

This study provided a theoretical basis for elucidating the pathogenesis and evaluating the prognosis of BLCA by screening potential biomarkers of BLCA.