Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures.
Journal
Cancer cell
ISSN
1878-3686
Date Issued
2025-07-30
Author(s)
Satpathy, Shankha
Clark, Natalie M
Chen, Yi-Ju
Hosseini, Noshad
Chang, Ya-Hsuan
Hsiao, Yi
Lei, Jonathan T
Petralia, Francesca
Geffen, Yifat
Heiman, David I
Paul, Indranil
Cho, Hanbyul
Hollenberg, Michelle
Marino, Giacomo B
Lin, Kuen-Tyng
Mannan, Rahul
White, C Jackson
Allen, Joe
Avanessian, Shayan C
Kane, M Harry
Wolfe, Ashley
Kinarivala, Miloni
Liu, Wenke
Anand, Shankara
Haines, Moe
Bergstrom, Erik J
Hussey, Grant
Li, Ginny Xiaohe
Mani, Deepak C
Fang, Hao
Jaehnig, Eric J
Keshishian, Hasmik
Miller, Brecca
Hsiao, Yi-Jing
Hsu, Kuo-Hsuan
Monovoukas, Alexi
Gohsman, Simone
Thorup, John R
Deng, Yamei
Akiyama, Yo
Deng, Eden
Sheng-Wen Chen, Eric
Krek, Azra
Espinoza, Rodrigo
Ma, Weiping
Charytonowicz, Daniel
Sebra, Robert
Lin, Jyun-Hong
Chen, Yan-Si
Hsu, Yin-Chen
Lin, Ze-Shiang
Chen, Kun-Chieh
Yeh, Chang-Wei
Wang, Yu-Tai
Lazar, Alexander J
Mesri, Mehdi
An, Eunkyung
Clauser, Karl R
Fenyö, David
Chinnaiyan, Arul M
Zhang, Bing
Ding, Li
Ruggles, Kelly
Newton, Chelsea
Zhang, Hui
Wang, Pei
Hostetter, Galen
Omenn, Gilbert S
Kumar-Sinha, Chandan
Thiagarajan, Mathangi
Govindan, Ramaswamy
Paik, Paul
Parolia, Abhijit
Li, Qing K
Ma'ayan, Avi
Getz, Gad A
Dhanasekaran, Saravana M
Robles, Ana I
Chang, Gee-Chen
Chen, Hsuan-Yu
Nesvizhskii, Alexey I
Carr, Steven A
Mani, D R
Cieslik, Marcin P
Chen, Yu-Ju
Gillette, Michael A
et al.
Abstract
Lung adenocarcinomas (LUAD) are a pressing global health problem with enduring lethality and rapidly shifting epidemiology. Proteogenomic studies integrating proteomics and post-translational modifications with genomics can identify clinical strata and oncogenic mechanisms, but have been underpowered to examine effects of ethnicity, smoking and environmental exposures, or sex on this heterogeneous disease. This comprehensive proteogenomic analysis of LUAD tumors and matched normal adjacent tissues from 406 patients across diverse geographic and demographic backgrounds explores the impact of understudied driver mutations, prognostic role of chromosomal instability, patterns of immune signaling, differential and sex-specific effects of endogenous mutagens and environmental carcinogens, and pathobiology of early-stage tumors with "late-like" characteristics. Candidate protein biomarkers are proposed for unstable tumors with highly fragmented genomes and for carcinogen exposures, and a LUAD subtype-specific atlas of therapeutic vulnerabilities is presented. These observations and the associated data resource advance the objective of precision management strategies for this devastating disease.
Subjects
CPTAC
ICPC
PTMs
biomarkers
genomics
lung adenocarcinoma
mass spectrometry
never-smokers
proteogenomics
smokers
SDGs
Publisher
Cell Press
Type
journal article