Desmocollin-3 and Bladder Cancer.

Abstract

Background: Desmocollin3, a transmembrane protein, is expressed in the basal/suprabasal layer of normal stratified epithelium. DSC3 gene expression is described in muscle-invasive bladder cancer (MIBC). DSC3-protein-expressing recurrent non-muscle-invasive bladder cancer (NMIBC) had a durable response to CADI-03, a DSC3-specific active immunotherapy.

Methods: We evaluated DSC3 protein expression and its correlation with tumor-infiltrating immune cells in bladder cancer. DSC3 gene expression and its correlation with 208 immune encoding genes, treatment outcome, and survival were evaluated using the "ARRAYEXPRESS" and "TCGA" datasets. Immune genes were grouped as tumor-controlling immune genes (TCIGs) and tumor-promoting immune genes (TPIGs) as per their functions.

Results & conclusions: NMIBC had higher DSC3 expression compared to MIBC. More immune genes were correlated with DSC3 in MIBC (21) compared to NMIBC (11). Amongst the TCIGs, six in NMIBC and one in MIBC had a negative correlation while two in NMIBC and nine in MIBC had a positive correlation with DSC3. Amongst the TPIGs, nine in NMIBC and five in MIBC had a negative correlation. Seven TPIGs had a positive correlation with DSC3 in MIBC and none in NMIBC. Of the T cell exhaustion markers, none were correlated with DSC3 in MIBC. Among NMIBC, CTLA4 and TIGIT were the only markers of exhaustion that demonstrated a negative correlation with DSC3. DSC3 expression was also higher in p53 mutant compared to wild p53, non-papillary MIBC compared to papillary MIBC, and in basal, squamous molecular subtype compared to luminal MIBC. MIBC with lower DSC3 expression had better outcomes (response, survival) compared to those with higher DSC3 expression.