Abstract 7013: Proteogenomic analysis identifies the association of cytoskeleton-related molecules with immunosuppressive state of small cell lung cancer

Abstract Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancers, defined by high proliferation rate, diagnosis at advanced stage, and quick relapse. The treatment regime of SCLC has not been changed from last four decades. Although FDA has recently approved the use of immune checkpoint inhibitor therapy for SCLC patients, the benefits are only marginal and limited to a subgroup of patients. Therefore, there is a significant need to explore the molecular mechanisms of immune suppression and utilize this knowledge to develop better therapies for SCLC patients. To understand the mechanisms of immune suppression in SCLC, we reanalyzed a publicly available proteogenomic dataset of 112 SCLC tumors and their adjacent normal tissues. We first utilizing immune signatures to divide samples into immune active (hot) and immune suppressed (cold) tumors. Cold tumors showed reduced overall survival compared to hot tumors. Pathway-based analysis of Genomic data identified the enrichment of mutations in the genes linked to cytoskeleton and motor activity. Similarly, analysis of proteomic data identified enrichment of proteins related to mRNA processing. Cytoskeleton and associated motor proteins are known to regulate mRNA processing. Therefore, further analysis of cytoskeleton-mediated regulation of mRNA processing may lead to the identification novel therapeutic targets. Citation Format: Dinesh K. Ahirwar, Beauty Kumari. Proteogenomic analysis identifies the association of cytoskeleton-related molecules with immunosuppressive state of small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7013.