Abstract B029: Desmocollin-3: a promising prognostic biomarker

Abstract Introduction: Desmocollin-3 (DSC3) is used for differentiating squamous lung cancer from non-squamous. Its expression is known to be altered in various cancers. Based on DSC3 gene expression cancers can be divided into two broad groups. Those with higher DSC3 gene level e.g. Squamous lung cancer (SCL), Head and Neck cancer (HNC), Cervical cancer (CEC) and those with lower DSC3 gene level e.g. Adenocarcinoma of lung (ACL), bladder cancer (BC), Renal cancer (REC), Uterine endometrial cancer (UEC) Stomach adenocarcinoma (STAC) . There is some evidence of DSC3 being prognostic biomarker for Squamous NSCLC (SCL). DSC3 is also a predictive biomarker for efficacy of Mycobacterium w (Mw) vaccine a heat-killed suspension of a non-pathogenic mycobacterium. The present study is focused on evaluating the gene expression levels of DSC3 and its impact on survival. Since it is known as one of the barrier molecules for tumor infiltration of immune cells, we also evaluated its impact along with DSC3 on survival using publicly available dataset. Materials and methods: SCL, HNC, CEC from a group of cancers with higher DSC3 gene level and ACL, BC, REC, UEC, STAC from a group of cancers with lower DSC3 gene level were evaluated for effect of DSC3 gene expression on Survival. Survival was evaluated for each cancer using PAN CANCER data base from K-M plotter using auto cut-off as well as upper and lower quartile. Effect of CD8+ cell, Treg cells, Macrophage, Th1, Th2, Neoantigen and mutation burden were also evaluated using the same platform and database. Results: In a group of cancer with higher DSC3 gene expression survival was found to be better in patients with higher DSC3 gene level. Hazard ratio (HR) for survival was 0.64 (p=0.0011) for SCL, 0.71(p=0.033) for HNC and 0.64(p=0.063) for CEC. In contrast, in a group of cancers with lower DSC3 gene expression, survival was poor with higher DSC3 gene level. HR was 1.97(p=8.6e06) for BC, 1.79(p=0.0065) for UEC, 1.66(0.00086) for REC, 1.66(p=0.0073) for STAC, 1.34 (p= 0.05) for ACL. DSC3 gene expression level was optimum for REC ACL and could not be improved further by combination of DSC3 gene expression level with other genes for immune parameters. Improved prognostication was observed when DSC3 gene expression level was evaluated along with following immune related genes. 1. CD8 enrichment in HNC (HR=0.63; p-0.029), BC (HR=2.53, p=1.10e-06), STAC (HR=2.68; p=0.00015). 2. decreased TH2 in SCL (HR=0.14;p=0.031), 3. lower mutation burden in CEC (HR=0.35 ;p=0.003 and ACL (HR=1.87;P=0.003) 4. macrophage enrichment in UEC (HR=6.87; p=6e04). Finding of this study needs to be validated. If confirmed, it may help in better segregation of patient as per baseline characteristic and potential treatment. Conclusion: DSC3 gene expression level may be useful in prognostication when used alone or with other immune parameters. This needs to be validated by evaluation of another independent cohort. Citation Format: Bakulesh Khamar, Arpit Dheeraj, Sanjay V. Malhotra. Desmocollin-3: a promising prognostic biomarker [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B029.