Abstract 1053: Cellular heterogeneity and stress response in lung tumors: understanding cancer disparities through spatial transcriptomics

Abstract Background: Despite having lower smoking rates, Black men have a higher incidence of lung cancer. Previously, we showed that social stressors, such as neighborhood violent crime, may influence tumor biology through stress response pathways. In this study, we investigated the relationship between neighborhood violent crime rates and glucocorticoid biosynthesis in lung tumors. Specifically, we examined how cell populations change in tumor regions with high glucocorticoid metabolism and receptor activity. Methods: We analyzed spatial transcriptomic data from 15 lung tumor samples. Pathway activity and cell type associations were examined using gene set co-regulation analysis (GESECA). We computed univariate and bivariate local Moran's I to assess spatial co-localization at p < 0.05. To validate these spatial associations, we performed unsupervised cell-type deconvolution using STdeconvolve and applied spatial interpolation to enhance the resolution of cell-type distributions. Results: We identified a positive correlation between neighborhood violent crime rates and glucocorticoid biosynthesis pathway activity (p < 0.05). Several epithelial cell types, including adventitial fibroblasts, basal cells, club cells, and mesothelial cells, were significantly associated with glucocorticoid biosynthesis-enriched regions in lung tumor samples from high-crime neighborhoods. Cell type deconvolution and spatial interpolation confirmed localized clustering of these epithelial cells within glucocorticoid biosynthesis-active regions at high resolution. Conclusions: Our findings suggest that social stressors, such as neighborhood violent crime, may contribute to lung cancer disparities by influencing tumor development through stress-induced pathways. This study highlights the importance of understanding cellular heterogeneity within the tumor microenvironment, which could inform targeted cancer prevention and control interventions. Citation Format: Sabrina Akter, Aiman Soliman, Zeynep Madak-Erdogan, Sage J. Kim. Cellular heterogeneity and stress response in lung tumors: understanding cancer disparities through spatial transcriptomics [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 1053.