Characterization of laminin-332 gene expression in molecular subtypes of human bladder cancer

Human bladder cancer (BCa) exhibits morphological and molecular heterogeneity which can complicate treatment. Morphologically, more than 90% of BCa is classified as urothelial cell carcinoma (UCC). Among other histological variants, UCC with squamous differentiation (SqD) shows a worse prognosis than pure UCC. In addition, basal-squamous BCa is enriched for SqD, and these tumors have a poor prognosis. Therefore, it is critical to elucidate the mechanisms to drive the basal-squamous phenotype of human BCa. Laminin-332 is a major glycoprotein of the epithelial basement membrane. It is well known that laminin-332 is a favorable target for extracellular matrix proteases such as matrix metalloproteinases (MMPs) in various diseases. Accumulating evidence indicates the significant role of laminin-332 in tumorigenesis. Here, we analyzed the expression of laminin-332 genes (LAMA3, LAMB3, LAMC2) in molecular subtypes of human BCa using publicly available data from The Cancer Genome Atlas (TCGA). Additionally, we also used q-RT-PCR to characterize laminin-332 gene expression between distinct molecular subtypes of human BCa cell lines. Our analysis of publicly available data show that laminin-332 genes are highly expressed in the basal-squamous molecular subtype of human BCa. In addition, we show laminin-332 genes are highly expressed in basal-squamous human BCa cell lines. Moreover, the expression of both LAMA3 and LAMC2 are negatively correlated with expression of the luminal transcription factor (TF) FOXA1 in the TCGA data. We also demonstrate that laminin-332 genes are downregulated by the overexpression of FOXA1 in a human basal-squamous BCa cell line (5637). Taken together, these results suggest that laminin-332 gene expression may be a biomarker of BCa patients with basal-squamous disease.