Abstract 5265: Investigating the role of Desmocollin-3 and immune infiltrate in bladder cancer
Authors: Shukla Chandreshwar P. , Jain Nayan K. , O'Donnell Michael A. , Vachhani Kapil J. , Patel Rashmi , Vanikar Aruna , Modi Rajiv I. , Malhotra Sanjay V. , Khamar Bakulesh 
Published: April 2023

Introduction: Adhesion molecules are important for tissue integrity, its maintenance as well as communication (signaling). Desmocollin-3 (DSC3) one of the desmosomal adhesion (Desmoglein 1, 2, 3 and Desmocollin 1, 2, 3) proteins is a trans-membrane glycoprotein present in basal/suprabasal layer of normal stratified epithelium. It is a p53-responsive desmosomal cadherin protein. Cancer development and progression are associated with either additional cytoplasmic expression of DSC3 as seen with squamous non-small cell lung cancer and colorectal cancer or loss of DSC3 expression as seen in prostate and breast cancer To investigate the role of DSC3 in bladder cancer, we evaluated the expression levels of DSC3 in biopsy samples of patients with non-muscle invasive bladder carcinoma (NMIBC) and muscle-invasive bladder carcinoma (MIBC) and correlated it with the clinical staging and immune cell infiltration. Also, its relationship with immune signature genes and immune cell subsets is evaluated using TCGA dataset available on c-bioportal.

Materials and Method: DSC3 protein expression was evaluated by Immunohistochemistry. H&E stained slides were evaluated by light microscopy to identify immune cells as macrophages or lymphocytes and their location as intrastromal or intratumoral as previously described. It was correlated with the type, stage, and grade of the tumor. Spearman correlation between DSC3 and 207 immune signature genes available in TCGA data was calculated using RSEM and methylation values of each gene.

Results: The data suggests that NMIBC is more likely to be DSC3 positive than MIBC. DSC3-positive samples are more likely to have tumor-infiltrating immune cells (TIL) compared to DSC3-negative samples. In silico analysis of bladder cancer shows that DSC3 mRNA expression is inversely proportional to its methylation. We found that DSC3 expression is biased towards the Th1 subset of immune cells. DSC3 is not correlated with PD-1/PDL1 expression, and the macrophage subsets are negatively correlated with DSC3.

Conclusion: DSC3 expression is associated with the Basal/Squamous type of bladder cancer. Therefore, this study suggests the potential of DSC3 as a predictive biomarker for response to systemic immunotherapy and resistance/poor response to conventional therapy (chemotherapy; radiotherapy, and cystectomy) and underscores the need for studies evaluating the potential of DSC3 expression as a biomarker.

Citation Format: Chandreshwar P. Shukla, Nayan K. Jain, Michael A. O'Donnell, Kapil J. Vachhani, Rashmi Patel, Aruna Vanikar, Rajiv I. Modi, Sanjay V. Malhotra, Bakulesh Khamar. Investigating the role of Desmocollin-3 and immune infiltrate in bladder cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5265.