Abstract 635: Unraveling the potential of neogenin 1 in non-small cell lung cancer: A path toward innovative combination therapies

Non-small cell lung cancer (NSCLC) has a poor survival rate due to delayed diagnosis and treatment resistance. Currently, immunotherapy has advanced the NSCLC treatment; however, only a small fraction of patients respond to the therapy, demanding the identification of novel biomarkers associated with resistance to develop new therapeutic strategies. Herein, we investigated the role of neogenin 1, a transmembrane protein that belongs to the immunoglobulin superfamily, in seven different human NSCLC cell lines and compared the expression with Jurkat T cell line and human peripheral blood mononuclear cell (PBMC)-derived CD3/CD28-activated CD8+ T cells using qPCR and western blot. We also performed the cell proliferation assay in adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) human cell lines after knockdown and overexpression of neogenin 1. We found that neogenin 1 was highly expressed in primary CD8+ T cells compared to the cancer cell lines, implying that genetic alteration of neogenin 1 might interfere more with CD8+ T cell effector function. We also discovered that both adenocarcinoma and squamous cell carcinoma cell proliferation ability were influenced by genetic alteration of neogenin 1. In addition, gene ontology enrichment analysis and KEGG pathway analysis indicated that neogenin 1 was involved in the TGF-beta signaling pathway, possibly suggesting that neogenin 1 might play a role in therapeutic resistance, including immunotherapy, in NSCLC. Correlation analysis in LUAD and LUSC in the TCGA dataset also revealed that neogenin 1 was positively correlated with a set of genes, such as IGF1R and USP8, associated with immunotherapy resistance. Further investigation of this potential gene in vivo will unfold its role in immunotherapy resistance in NSCLC, paving the way for developing novel and effective combinatorial therapeutic strategies targeting neogenin 1. Citation Format: Asmita Pandey, Shaoqiu Chen, Li Ma, Mayumi Jijiwa, Masaki Nasu, Vedbar Khadka, Yu Chen, Hua Yang, Sudhir Rai, Youping Deng. Unraveling the potential of neogenin 1 in non-small cell lung cancer: A path toward innovative combination therapies [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 635.