Bioinformatics analysis and clinical validation identify FBXW9 as a biomarker in bladder urothelial carcinoma

F-box and WD repeat domain-containing protein 9 (FBXW9), a member of the F-box protein family, is dysregulated and involved in the progression of human malignancies. However, its functional mechanisms and clinical significance in bladder urothelial carcinoma (BLCA) remain poorly understood. This study aimed to systematically investigate the diagnostic and prognostic value of FBXW9 in BLCA.

Data obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were utilized to examine the differential expression of FBXW9 in BLCA tissues compared to adjacent normal tissues. These findings were further validated through immunohistochemical (IHC) staining of clinical tissue samples. In order to explore the possible biological roles and signaling pathways of FBXW9 in BLCA, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were utilized. Genetic alterations and methylation profiles of FBXW9 were examined via MethSurv and cBioPortal databases. The relationship between the expression of FBXW9 and the infiltration of tumor immune cells was analyzed utilizing the Tumor IMmune Estimation Resource (TIMER) algorithm.

FBXW9 was significantly upregulated in BLCA. Elevated FBXW9 levels were correlated with more advanced clinicopathological stages. Kaplan-Meier survival analysis demonstrated that high FBXW9 expression was associated with significantly shorter overall survival (OS) and disease-specific survival (DSS). Analysis of functional enrichment indicated that genes associated with FBXW9 were significantly involved in key pathways such as the cell cycle and DNA synthesis. Furthermore, FBXW9 expression showed a significant correlation with the infiltration levels of multiple immune cell subtypes, notably T helper 2 (Th2) cells, γδT cells, and plasmacytoid dendritic cells (pDCs).

FBXW9 is significantly upregulated in BLCA and correlates with advanced clinicopathological stages. Elevated FBXW9 expression is associated with unfavorable prognosis in univariate analysis and shows significant correlations with immune cell infiltration. FBXW9 shows promise as a potential diagnostic biomarker and warrants further investigation for therapeutic targeting.