Prognostic value and association with epithelial-mesenchymal transition and molecular subtypes of the proteoglycan biglycan in advanced bladder cancer

Objective: Dysregulation of the extracellular matrix molecule biglycan (BGN) predicts poor survival in several cancer entities. Our study investigated the prognostic impact of BGN in bladder cancer (BC) in 2 independent cohorts and assessed its role in epithelial-mesenchymal transition (EMT) and association with molecular BC subtypes. Methods: BGN protein expression was correlated with the oncological outcome of 162 patients with BC undergoing radical cystectomy (RC) in a single center and furthermore on gene expression level in the TCGA database. Cut-off values for BGN protein and RNA expression were tested with receiver operating characteristic (ROC) curves. BGN gene expression was correlated with established EMT and BC gene signatures in the TCGA database using gene set enrichment analysis (GSEA). Key EMT and basal/luminal molecular BC subtype markers were correlated with BGN expression and data were shown in a heat map. Results: BGN upregulation in BC cells on the protein level predicted poor oncological survival in the institutional cohort for both univariate (P = 0.007) and multivariate (P = 0.040) analyses. BGN expression was not associated with other clinicopathological parameters. The prognostic value of BGN was validated on the mRNA level in the BC TCGA database (P = 0.002). Both EMT and BC core gene signatures (P < 0.001) correlated with BGN expression in GSEA. BGN gene expression was associated with key indicators of EMT. BGN was associated positively with the molecular basal BC subtype and negatively with the BC luminal subtype. Conclusion: BGN is an independent prognosticator for poor survival in BC patients. BGN is associated with the basal molecular BC subtype. EMT might be a key player for BGN driven oncogenesis, as BGN expression correlates with EMT gene signatures. (C) 2019 Elsevier Inc. All rights reserved.