Abstract 3204: Differential expression of angiogenesis-associated genes in smoker and non-smoker lung adenocarcinoma patients

Abstract

Abstract Tobacco smoke (TS) is one of the most prominent risk factors for lung and several other malignancies. Toxic chemicals present in TS induce DNA damage leading to carcinogenic mutations. Moreover, TS can also cause epigenetic and gene expression changes in tumor and other cells of the tumor microenvironment, especially through its addictive component nicotine. We and others have reported that nicotine promotes tumor angiogenesis via its direct impact on the endothelial cells or by altering the cancer cell secretome. In this study, we wanted to explore the association of smoking habits with the differential expression of angiogenesis-related genes in lung adenocarcinoma (LUAD) patients. Gene Set Enrichment Analysis (GSEA) identified a set of 48 angiogenesis-related genes that were surveyed for differential expression in smoker versus non-smoker patients in The Cancer Genomic Atlas (TCGA) database using an interactive web application, UALCAN. Gender and age of the LUAD patients were considered as confounding variables since patients of different age groups and gender can have biological and physiological differences, which could influence gene expression regardless of the smoking habits. We identified a total of fourteen differentially-expressed genes, of which four (HTATIP2, NCL, SPHK1, and VEGFA) were overexpressed and ten (AGGF1, AMOT, C1GALT1, ERAP1, NPR1, PML, RNH1, SHH, SPINL5, and TNFSF12) were downregulated in LUAD of smokers than those of non-smokers. Five of the differentially-expressed genes (HTATIP2, NCL NPR1, PML, and TNFSF12) exhibited significantly different transcript levels in males versus females and three (SPHK1, AGGF1, and SPINK5) showed varying pattern of expression in LUAD of different age group patients. Literature survey found prior published evidence for an association of two of the fourteen differentially expressed genes (NCL and NPR) with nicotine exposure. Together, our findings identify smoking-associated angiogenic gene signatures that could be potential effectors of nicotine signaling that promotes cancer angiogenesis and should be validated further by conducting laboratory investigations. Citation Format: Shubhangi Singh, Santanu Dasgupta, Elba A. Turbat-Herrera, Seema Singh, Ajay P. Singh. Differential expression of angiogenesis-associated genes in smoker and non-smoker lung adenocarcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3204.