Abstract 5687: Immune-associated genes as potential therapeutic targets in small cell lung cancer

Abstract Background: Recently, immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of small cell lung cancer (SCLC). While their development has enhanced treatment options for SCLC, the effectiveness of immunotherapy remains limited due to the low expression of Programmed Cell Death Ligand 1 (PD-L1) and the emergence of immunotherapy resistance. As a result, there is a pressing need for new biomarkers to guide SCLC treatment. Methods: We obtained four microarray datasets from GEO (Gene Expression Omnibus) database and screened differentially expressed genes (DEGs). After the establishment of protein-protein interaction network through Cytoscape, key hub genes were selected via a volcano plot. To validate these results, we used an independent dataset as a test cohort. We also analyzed differences in immune cell infiltration between normal and SCLC samples. Lastly, we identified a marker gene associated with immune cell infiltration and validated its role in SCLC through in vitro experiments. Results: We screened GEO gene expression database for DEGs, which are immune-related genes, in SCLC. A PPI network analysis revealed seven overexpressed hub genes (AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, AURKA) in the SCLC cohort, which were significantly more expressed than in normal cells. Correlation analysis between immune cells and the seven hub genes showed that BIRC5 expression was inversely correlated with monocytes. In SCLC cell lines such as SBC5 and SBC3, downregulation of BIRC5 using siRNA induced apoptosis and inhibited cell activity, tumor invasiveness and proliferative potential. Furthermore, treatment with a BIRC5 inhibitor (YM155) reduced SCLC cell viability and increased apoptosis. Co-culture experiments with SBC3 and monocytes (e.g., THP1) led to decreased BIRC5 expression in SBC3 cells. Conclusion: We identified AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, and AURKA genes as potential immune-related therapeutic targets for SCLC. In particular, high BIRC5 expression promotes SCLC progression and may influence the immune microenvironment of the tumor by affecting monocytes. Citation Format: Akihiko Miyanaga, Yang Yunchu, Kuniko Matsuda, Takehiro Tozuka, Aya Fukuizumi, Kakeru Hisakane, Naomi Onda, Susumu Takeuchi, Koichiro Kamio, Kazuo Kasahara, Masahiro Seike. Immune-associated genes as potential therapeutic targets in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5687.