Abstract 102: Identifying predictors of liver metastasis in small cell lung cancer using gene expression profiling

Abstract Small cell lung cancer (SCLC) is a highly aggressive, treatment-resistant form of lung cancer which carries an exceptionally poor prognosis. Patients with SCLC often present at an advanced stage due to the propensity of SCLC for early metastasis, with common sites including the brain, liver, adrenal glands, and bone. Liver metastasis has been identified as an independent prognostic factor for unfavorable response to chemotherapy, but specific steps in the liver metastatic cascade are yet to be described. Here, we seek to better characterize SCLC liver metastases by analyzing gene expression data from cell lines and patient biopsy samples. We analyzed data published in MetMap (Jin et al., 2020), which estimated organ-specific ‘metastatic potential’ of a variety of cell lines from the Cancer Cell Line Encyclopedia (CCLE). Gene set enrichment analysis revealed that SCLC cell lines with high liver metastatic potential exhibit significant positive enrichment of MYC signaling, oxidative phosphorylation, and Wnt/Beta-catenin signaling with negative enrichment of TNF-alpha signaling, inflammatory response, interferon response, and epithelial-to-mesenchymal transition. This pattern appears unique to SCLC cells compared with liver metastatic non-small cell lung cancer and colorectal cancer cells. Genes with differentially higher expression in SCLC lines with high liver metastatic potential were also found to play roles in embryonic organ and lung development. Cell lines with low liver metastatic potential exhibited increased expression of genes involved in pathways related to natural killer (NK) cell mediated immunity, suggesting the important role for innate immunity in preventing liver metastasis. This observation was confirmed in multiple datasets of SCLC patient biopsies, with higher expression of NK cell activating genes associated with a more favorable prognosis. Additionally, chromosome 3p deletion was more frequently observed in liver metastatic cell lines, and in primary patient tumors, the presence of a 3p deletion (plus 5q non-deletion) was associated with the presence of liver metastasis. Genes and pathways identified by this analysis, following experimental validation, could serve as potential therapeutic targets to predict and disrupt the liver metastatic cascade. Citation Format: George Chrisafis, Mohit Arora, Nobuyuki Takahashi, Anish Thomas. Identifying predictors of liver metastasis in small cell lung cancer using gene expression profiling [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 102.