Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities

• DOI: 10.7554/elife.95453
• Publication Date: 2024-05-31T10:32:12Z
• Authors: Honglei Zhang; Chao Liu; Shuting Wang; Qing Wang; Xu Feng; Huawei Jiang; Li Xiao; Chao Luo; Lu Zhang; Fei Hou; Minjun Zhou; Zhiyong Deng; Heng Li; Yong Zhang; Xiaosan Su; Gaofeng Li
• Keywords: Targeted Therapy

Air pollution significantly impacts lung cancer progression, but there is a lack of comprehensive molecular characterization clinical samples associated with air pollution. Here, we performed proteogenomic analysis adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke primary contributor to high incidence. Genomic mutation revealed XWLC as distinct subtype LUAD separate cases smoking or endogenous factors. Mutational signature suggested that Benzo[a]pyrene (BaP) major risk factor XWLC. The BaP-induced hotspot, EGFR-G719X, was present 20% which endowed elevated MAPK pathway activations and worse outcomes compared common EGFR mutations. Multi-omics clustering identified four clinically relevant subtypes. These subgroups exhibited features biological processes, genetic alterations, metabolism demands, immune landscape, radiomic features. Finally, MAD1 TPRN were novel potential therapeutic targets Our study provides valuable resource for researchers clinicians explore prevention treatment strategies air-pollution-associated cancers.