Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures

Shankha Satpathy; Natalie M. Clark; Yi Ju Chen; Noshad Hosseini; Ya Hsuan Chang; Yi Hsiao; Jonathan T. Lei; Francesca Petralia; Jin Shing Chen; Yifat Geffen; David I. Heiman; Indranil Paul; Hanbyul Cho; Michelle Hollenberg; Giacomo B. Marino; Kuen Tyng Lin; Rahul Mannan; C. Jackson White; Joe Allen; Shayan C. Avanessian; M. Harry Kane; Ashley Wolfe; Miloni Kinarivala; Wenke Liu; Shankara Anand; Mong Wei Lin; Moe Haines; Erik J. Bergstrom; Grant Hussey; Ginny Xiaohe Li; Deepak C. Mani; Hao Fang; Eric J. Jaehnig; Hasmik Keshishian; Brecca Miller; Kang Yi Su; Yi Jing Hsiao; Hsao Hsun Hsu; Min Shu Hsieh; Kuo Hsuan Hsu; Alexi Monovoukas; Simone Gohsman; John R. Thorup; Yamei Deng; Yo Akiyama; Eden Deng; Eric Sheng-Wen Chen; Azra Krek; Rodrigo Espinoza; Weiping Ma; Daniel Charytonowicz; Robert Sebra; Jyun Hong Lin; Yan Si Chen; Yin Chen Hsu; Ze Shiang Lin; Kun Chieh Chen; Chang Wei Yeh; Yu Tai Wang; Alexander J. Lazar; Mehdi Mesri; Eunkyung An; Xu Zhang; Karl R. Clauser; David Fenyö; Arul M. Chinnaiyan; Bing Zhang; Li Ding; Kelly Ruggles; Chelsea Newton; Hui Zhang; Pei Wang; Galen Hostetter; Gilbert S. Omenn; Chandan Kumar-Sinha; Mathangi Thiagarajan; Ramaswamy Govindan; Paul Paik; Abhijit Parolia; Qing K. Li; Avi Ma'ayan; Gad A. Getz; Saravana M. Dhanasekaran; Ana I. Robles; Gee Chen Chang; Pan Chyr Yang; Sung Liang Yu; Hsuan Yu Chen; Alexey I. Nesvizhskii; Steven A. Carr; D. R. Mani; Marcin P. Cieslik; Yu Ju Chen; Michael A. Gillette; Chao Wen Lu; Cheng Hsiang Chu; Chi Ya Shen; Chia Li Han; Chien Chia Lin; Chien Yu Lin; Ching Wen Chen; Chung Hsien Lin; Hsiang En Hsu; Hsing Jui Tsai; Jia Jun Wu; Jing Wei Lin; Juani Waniwan; Ki Hok Liao; Pei Hsing Chen; Pei Rong Huang; Sin Ming Huang; Tai Ching Lin; Wan Chun Lai; Wei Tzu Chiu; Xu Heng Chiang; Ya Ling Chang; Yan Ming Chen; Yi Ling Chen; Yi Wen Wang; Yi Wei Lin; Yu Cheng Chang; Yu Ting Huang; Yuju Lien; Zhe Rong Zheng; Abdul Samad Hashimi; Adrij Mohan; Akhilesh Pandey; Alexander Pilozzi; Alex Webster; Amanda G. Paulovich; Aniket Dagar; Andrew K. Godwin; Barbara Pruetz; Bart O. Williams; Brian J. Druker; Daniel C. Rohrer; Daniel W. Chan; Danail Petrov; David Chesla; Diwakar Davaar; Elizabeth Duffy; George D. Wilson; Grace Zhao; Iga Kołodziejczak; Jan Lubinski; Jasmine Huang; Jason Hafron; Jeffrey W. Tyner; John Koomen; Kakhaber Zaalishvili; Karen A. Ketchum; Maciej Wiznerowicz; Marcin J. Domagalski; Meenakshi Anurag; Melissa Borucki; Nathan J. Edwards; Negin Vatanian; Pamela Grady; Paul D. Piehowski; Popovici Bogdan; Qin Li; Rafael Fonseca; Rashna Madan; Ratna R. Thangudu; Reese Crispen; Ronald Matteotti; Ross Bremner; Sandra Cerda; Sandra L. Cottingham; Shirley Tsang; Shuang Cai; Tao Liu; Thomas Bauer; William W. Maggio; Xiaojun Jing; Yuping Zhang; Yvonne Shutack; Zoran Andric

doi:10.1016/j.ccell.2025.07.011

Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures

Shankha Satpathy
, Natalie M. Clark
, Yi Ju Chen
, Noshad Hosseini
, Ya Hsuan Chang
, Yi Hsiao
, Jonathan T. Lei
, Francesca Petralia
, Jin Shing Chen
, Yifat Geffen
, David I. Heiman
, Indranil Paul
, Hanbyul Cho
, Michelle Hollenberg
, Giacomo B. Marino
, Kuen Tyng Lin
, Rahul Mannan
, C. Jackson White
, Joe Allen
, Shayan C. Avanessian

M. Harry Kane, Ashley Wolfe, Miloni Kinarivala, Wenke Liu, Shankara Anand, Mong Wei Lin, Moe Haines, Erik J. Bergstrom, Grant Hussey, Ginny Xiaohe Li, Deepak C. Mani, Hao Fang, Eric J. Jaehnig, Hasmik Keshishian, Brecca Miller, Kang Yi Su, Yi Jing Hsiao, Hsao Hsun Hsu, Min Shu Hsieh, Kuo Hsuan Hsu, Alexi Monovoukas, Simone Gohsman, John R. Thorup, Yamei Deng, Yo Akiyama, Eden Deng, Eric Sheng-Wen Chen, Azra Krek, Rodrigo Espinoza, Weiping Ma, Daniel Charytonowicz, Robert Sebra, Jyun Hong Lin, Yan Si Chen, Yin Chen Hsu, Ze Shiang Lin, Kun Chieh Chen, Chang Wei Yeh, Yu Tai Wang, Alexander J. Lazar, Mehdi Mesri, Eunkyung An, Xu Zhang, Karl R. Clauser, David Fenyö, Arul M. Chinnaiyan, Bing Zhang, Li Ding, Kelly Ruggles, Chelsea Newton, Hui Zhang, Pei Wang, Galen Hostetter, Gilbert S. Omenn, Chandan Kumar-Sinha, Mathangi Thiagarajan, Ramaswamy Govindan, Paul Paik, Abhijit Parolia, Qing K. Li, Avi Ma'ayan, Gad A. Getz, Saravana M. Dhanasekaran, Ana I. Robles, Gee Chen Chang, Pan Chyr Yang, Sung Liang Yu, Hsuan Yu Chen, Alexey I. Nesvizhskii, Steven A. Carr, D. R. Mani, Marcin P. Cieslik, Yu Ju Chen, Michael A. Gillette, Chao Wen Lu, Cheng Hsiang Chu, Chi Ya Shen, Chia Li Han, Chien Chia Lin, Chien Yu Lin, Ching Wen Chen, Chung Hsien Lin, Hsiang En Hsu, Hsing Jui Tsai, Jia Jun Wu, Jing Wei Lin, Juani Waniwan, Ki Hok Liao, Pei Hsing Chen, Pei Rong Huang, Sin Ming Huang, Tai Ching Lin, Wan Chun Lai, Wei Tzu Chiu, Xu Heng Chiang, Ya Ling Chang, Yan Ming Chen, Yi Ling Chen, Yi Wen Wang, Yi Wei Lin, Yu Cheng Chang, Yu Ting Huang, Yuju Lien, Zhe Rong Zheng, Abdul Samad Hashimi, Adrij Mohan, Akhilesh Pandey, Alexander Pilozzi, Alex Webster, Amanda G. Paulovich, Aniket Dagar, Andrew K. Godwin, Barbara Pruetz, Bart O. Williams, Brian J. Druker, Daniel C. Rohrer, Daniel W. Chan, Danail Petrov, David Chesla, Diwakar Davaar, Elizabeth Duffy, George D. Wilson, Grace Zhao, Iga Kołodziejczak, Jan Lubinski, Jasmine Huang, Jason Hafron, Jeffrey W. Tyner, John Koomen, Kakhaber Zaalishvili, Karen A. Ketchum, Maciej Wiznerowicz, Marcin J. Domagalski, Meenakshi Anurag, Melissa Borucki, Nathan J. Edwards, Negin Vatanian, Pamela Grady, Paul D. Piehowski, Popovici Bogdan, Qin Li, Rafael Fonseca, Rashna Madan, Ratna R. Thangudu, Reese Crispen, Ronald Matteotti, Ross Bremner, Sandra Cerda, Sandra L. Cottingham, Shirley Tsang, Shuang Cai, Tao Liu, Thomas Bauer, William W. Maggio, Xiaojun Jing, Yuping Zhang, Yvonne Shutack, Zoran Andric

School of Medicine

Broad Institute
Academia Sinica Taiwan HQ
University of Michigan, Ann Arbor
National Health Research Institutes Taiwan
Baylor College of Medicine
Icahn School of Medicine at Mount Sinai
National Taiwan University
Massachusetts General Hospital
New York University
Veterans General Hospital-Taichung Taiwan
Chung Shan Medical University
National Applied Research Laboratories Taiwan
University of Texas MD Anderson Cancer Center
National Institutes of Health
Washington University St. Louis
Van Andel Institute
Johns Hopkins University
Leidos Inc
Memorial Sloan-Kettering Cancer Center
Cornell University
National Chung Hsing University

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English
Pages (from-to)	1731-1757.e17
Journal	Cancer Cell
Volume	43
Issue number	9
DOIs	https://doi.org/10.1016/j.ccell.2025.07.011
State	Published - 8 Sep 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CPTAC
ICPC
PTMs
biomarkers
genomics
lung adenocarcinoma
mass spectrometry
never-smokers
proteogenomics
smokers

Access to Document

10.1016/j.ccell.2025.07.011

Cite this

Satpathy, S., Clark, N. M., Chen, Y. J., Hosseini, N., Chang, Y. H., Hsiao, Y., Lei, J. T., Petralia, F., Chen, J. S., Geffen, Y., Heiman, D. I., Paul, I., Cho, H., Hollenberg, M., Marino, G. B., Lin, K. T., Mannan, R., White, C. J., Allen, J., ... Andric, Z. (2025). Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures. Cancer Cell, 43(9), 1731-1757.e17. https://doi.org/10.1016/j.ccell.2025.07.011

@article{caec56f05678409db3700b248efcefe2,

title = "Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures",

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 {\textquotedblleft}late-like{\textquotedblright} 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.",

keywords = "CPTAC, ICPC, PTMs, biomarkers, genomics, lung adenocarcinoma, mass spectrometry, never-smokers, proteogenomics, smokers",

author = "Shankha Satpathy and Clark, \{Natalie M.\} and Chen, \{Yi Ju\} and Noshad Hosseini and Chang, \{Ya Hsuan\} and Yi Hsiao and Lei, \{Jonathan T.\} and Francesca Petralia and Chen, \{Jin Shing\} and Yifat Geffen and Heiman, \{David I.\} and Indranil Paul and Hanbyul Cho and Michelle Hollenberg and Marino, \{Giacomo B.\} and Lin, \{Kuen Tyng\} and Rahul Mannan and White, \{C. Jackson\} and Joe Allen and Avanessian, \{Shayan C.\} and Kane, \{M. Harry\} and Ashley Wolfe and Miloni Kinarivala and Wenke Liu and Shankara Anand and Lin, \{Mong Wei\} and Moe Haines and Bergstrom, \{Erik J.\} and Grant Hussey and Li, \{Ginny Xiaohe\} and Mani, \{Deepak C.\} and Hao Fang and Jaehnig, \{Eric J.\} and Hasmik Keshishian and Brecca Miller and Su, \{Kang Yi\} and Hsiao, \{Yi Jing\} and Hsu, \{Hsao Hsun\} and Hsieh, \{Min Shu\} and Hsu, \{Kuo Hsuan\} and Alexi Monovoukas and Simone Gohsman and Thorup, \{John R.\} and Yamei Deng and Yo Akiyama and Eden Deng and \{Sheng-Wen Chen\}, Eric and Azra Krek and Rodrigo Espinoza and Weiping Ma and Daniel Charytonowicz and Robert Sebra and Lin, \{Jyun Hong\} and Chen, \{Yan Si\} and Hsu, \{Yin Chen\} and Lin, \{Ze Shiang\} and Chen, \{Kun Chieh\} and Yeh, \{Chang Wei\} and Wang, \{Yu Tai\} and Lazar, \{Alexander J.\} and Mehdi Mesri and Eunkyung An and Xu Zhang and Clauser, \{Karl R.\} and David Feny{\"o} and Chinnaiyan, \{Arul M.\} and Bing Zhang and Li Ding and Kelly Ruggles and Chelsea Newton and Hui Zhang and Pei Wang and Galen Hostetter and Omenn, \{Gilbert S.\} and Chandan Kumar-Sinha and Mathangi Thiagarajan and Ramaswamy Govindan and Paul Paik and Abhijit Parolia and Li, \{Qing K.\} and Avi Ma'ayan and Getz, \{Gad A.\} and Dhanasekaran, \{Saravana M.\} and Robles, \{Ana I.\} and Chang, \{Gee Chen\} and Yang, \{Pan Chyr\} and Yu, \{Sung Liang\} and Chen, \{Hsuan Yu\} and Nesvizhskii, \{Alexey I.\} and Carr, \{Steven A.\} and Mani, \{D. R.\} and Cieslik, \{Marcin P.\} and Chen, \{Yu Ju\} and Gillette, \{Michael A.\} and Lu, \{Chao Wen\} and Chu, \{Cheng Hsiang\} and Shen, \{Chi Ya\} and Han, \{Chia Li\} and Lin, \{Chien Chia\} and Lin, \{Chien Yu\} and Chen, \{Ching Wen\} and Lin, \{Chung Hsien\} and Hsu, \{Hsiang En\} and Tsai, \{Hsing Jui\} and Wu, \{Jia Jun\} and Lin, \{Jing Wei\} and Juani Waniwan and Liao, \{Ki Hok\} and Chen, \{Pei Hsing\} and Huang, \{Pei Rong\} and Huang, \{Sin Ming\} and Lin, \{Tai Ching\} and Lai, \{Wan Chun\} and Chiu, \{Wei Tzu\} and Chiang, \{Xu Heng\} and Chang, \{Ya Ling\} and Chen, \{Yan Ming\} and Chen, \{Yi Ling\} and Wang, \{Yi Wen\} and Lin, \{Yi Wei\} and Chang, \{Yu Cheng\} and Huang, \{Yu Ting\} and Yuju Lien and Zheng, \{Zhe Rong\} and Hashimi, \{Abdul Samad\} and Adrij Mohan and Akhilesh Pandey and Alexander Pilozzi and Alex Webster and Paulovich, \{Amanda G.\} and Aniket Dagar and Godwin, \{Andrew K.\} and Barbara Pruetz and Williams, \{Bart O.\} and Druker, \{Brian J.\} and Rohrer, \{Daniel C.\} and Chan, \{Daniel W.\} and Danail Petrov and David Chesla and Diwakar Davaar and Elizabeth Duffy and Wilson, \{George D.\} and Grace Zhao and Iga Ko{\l}odziejczak and Jan Lubinski and Jasmine Huang and Jason Hafron and Tyner, \{Jeffrey W.\} and John Koomen and Kakhaber Zaalishvili and Ketchum, \{Karen A.\} and Maciej Wiznerowicz and Domagalski, \{Marcin J.\} and Meenakshi Anurag and Melissa Borucki and Edwards, \{Nathan J.\} and Negin Vatanian and Pamela Grady and Piehowski, \{Paul D.\} and Popovici Bogdan and Qin Li and Rafael Fonseca and Rashna Madan and Thangudu, \{Ratna R.\} and Reese Crispen and Ronald Matteotti and Ross Bremner and Sandra Cerda and Cottingham, \{Sandra L.\} and Shirley Tsang and Shuang Cai and Tao Liu and Thomas Bauer and Maggio, \{William W.\} and Xiaojun Jing and Yuping Zhang and Yvonne Shutack and Zoran Andric",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = sep,

day = "8",

doi = "10.1016/j.ccell.2025.07.011",

language = "English",

volume = "43",

pages = "1731--1757.e17",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "9",

}

Satpathy, S, Clark, NM, Chen, YJ, Hosseini, N, Chang, YH, Hsiao, Y, Lei, JT, Petralia, F, Chen, JS, Geffen, Y, Heiman, DI, Paul, I, Cho, H, Hollenberg, M, Marino, GB, Lin, KT, Mannan, R, White, CJ, Allen, J, Avanessian, SC, Kane, MH, Wolfe, A, Kinarivala, M, Liu, W, Anand, S, Lin, MW, Haines, M, Bergstrom, EJ, Hussey, G, Li, GX, Mani, DC, Fang, H, Jaehnig, EJ, Keshishian, H, Miller, B, Su, KY, Hsiao, YJ, Hsu, HH, Hsieh, MS, Hsu, KH, Monovoukas, A, Gohsman, S, Thorup, JR, Deng, Y, Akiyama, Y, Deng, E, Sheng-Wen Chen, E, Krek, A, Espinoza, R, Ma, W, Charytonowicz, D, Sebra, R, Lin, JH, Chen, YS, Hsu, YC, Lin, ZS, Chen, KC, Yeh, CW, Wang, YT, Lazar, AJ, Mesri, M, An, E, Zhang, X, Clauser, KR, Fenyö, D, Chinnaiyan, AM, Zhang, B, Ding, L, Ruggles, K, Newton, C, Zhang, H, Wang, P, Hostetter, G, Omenn, GS, Kumar-Sinha, C, Thiagarajan, M, Govindan, R, Paik, P, Parolia, A, Li, QK, Ma'ayan, A, Getz, GA, Dhanasekaran, SM, Robles, AI, Chang, GC, Yang, PC, Yu, SL, Chen, HY, Nesvizhskii, AI, Carr, SA, Mani, DR, Cieslik, MP, Chen, YJ, Gillette, MA, Lu, CW, Chu, CH, Shen, CY, Han, CL, Lin, CC, Lin, CY, Chen, CW, Lin, CH, Hsu, HE, Tsai, HJ, Wu, JJ, Lin, JW, Waniwan, J, Liao, KH, Chen, PH, Huang, PR, Huang, SM, Lin, TC, Lai, WC, Chiu, WT, Chiang, XH, Chang, YL, Chen, YM, Chen, YL, Wang, YW, Lin, YW, Chang, YC, Huang, YT, Lien, Y, Zheng, ZR, Hashimi, AS, Mohan, A, Pandey, A, Pilozzi, A, Webster, A, Paulovich, AG, Dagar, A, Godwin, AK, Pruetz, B, Williams, BO, Druker, BJ, Rohrer, DC, Chan, DW, Petrov, D, Chesla, D, Davaar, D, Duffy, E, Wilson, GD, Zhao, G, Kołodziejczak, I, Lubinski, J, Huang, J, Hafron, J, Tyner, JW, Koomen, J, Zaalishvili, K, Ketchum, KA, Wiznerowicz, M, Domagalski, MJ, Anurag, M, Borucki, M, Edwards, NJ, Vatanian, N, Grady, P, Piehowski, PD, Bogdan, P, Li, Q, Fonseca, R, Madan, R, Thangudu, RR, Crispen, R, Matteotti, R, Bremner, R, Cerda, S, Cottingham, SL, Tsang, S, Cai, S, Liu, T, Bauer, T , Maggio, WW, Jing, X, Zhang, Y, Shutack, Y & Andric, Z 2025, 'Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures', Cancer Cell, vol. 43, no. 9, pp. 1731-1757.e17. https://doi.org/10.1016/j.ccell.2025.07.011

TY - JOUR

T1 - Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures

AU - Satpathy, Shankha

AU - Clark, Natalie M.

AU - Chen, Yi Ju

AU - Hosseini, Noshad

AU - Chang, Ya Hsuan

AU - Hsiao, Yi

AU - Lei, Jonathan T.

AU - Petralia, Francesca

AU - Chen, Jin Shing

AU - Geffen, Yifat

AU - Heiman, David I.

AU - Paul, Indranil

AU - Cho, Hanbyul

AU - Hollenberg, Michelle

AU - Marino, Giacomo B.

AU - Lin, Kuen Tyng

AU - Mannan, Rahul

AU - White, C. Jackson

AU - Allen, Joe

AU - Avanessian, Shayan C.

AU - Kane, M. Harry

AU - Wolfe, Ashley

AU - Kinarivala, Miloni

AU - Liu, Wenke

AU - Anand, Shankara

AU - Lin, Mong Wei

AU - Haines, Moe

AU - Bergstrom, Erik J.

AU - Hussey, Grant

AU - Li, Ginny Xiaohe

AU - Mani, Deepak C.

AU - Fang, Hao

AU - Jaehnig, Eric J.

AU - Keshishian, Hasmik

AU - Miller, Brecca

AU - Su, Kang Yi

AU - Hsiao, Yi Jing

AU - Hsu, Hsao Hsun

AU - Hsieh, Min Shu

AU - Hsu, Kuo Hsuan

AU - Monovoukas, Alexi

AU - Gohsman, Simone

AU - Thorup, John R.

AU - Deng, Yamei

AU - Akiyama, Yo

AU - Deng, Eden

AU - Sheng-Wen Chen, Eric

AU - Krek, Azra

AU - Espinoza, Rodrigo

AU - Ma, Weiping

AU - Charytonowicz, Daniel

AU - Sebra, Robert

AU - Lin, Jyun Hong

AU - Chen, Yan Si

AU - Hsu, Yin Chen

AU - Lin, Ze Shiang

AU - Chen, Kun Chieh

AU - Yeh, Chang Wei

AU - Wang, Yu Tai

AU - Lazar, Alexander J.

AU - Mesri, Mehdi

AU - An, Eunkyung

AU - Zhang, Xu

AU - Clauser, Karl R.

AU - Fenyö, David

AU - Chinnaiyan, Arul M.

AU - Zhang, Bing

AU - Ding, Li

AU - Ruggles, Kelly

AU - Newton, Chelsea

AU - Zhang, Hui

AU - Wang, Pei

AU - Hostetter, Galen

AU - Omenn, Gilbert S.

AU - Kumar-Sinha, Chandan

AU - Thiagarajan, Mathangi

AU - Govindan, Ramaswamy

AU - Paik, Paul

AU - Parolia, Abhijit

AU - Li, Qing K.

AU - Ma'ayan, Avi

AU - Getz, Gad A.

AU - Dhanasekaran, Saravana M.

AU - Robles, Ana I.

AU - Chang, Gee Chen

AU - Yang, Pan Chyr

AU - Yu, Sung Liang

AU - Chen, Hsuan Yu

AU - Nesvizhskii, Alexey I.

AU - Carr, Steven A.

AU - Mani, D. R.

AU - Cieslik, Marcin P.

AU - Chen, Yu Ju

AU - Gillette, Michael A.

AU - Lu, Chao Wen

AU - Chu, Cheng Hsiang

AU - Shen, Chi Ya

AU - Han, Chia Li

AU - Lin, Chien Chia

AU - Lin, Chien Yu

AU - Chen, Ching Wen

AU - Lin, Chung Hsien

AU - Hsu, Hsiang En

AU - Tsai, Hsing Jui

AU - Wu, Jia Jun

AU - Lin, Jing Wei

AU - Waniwan, Juani

AU - Liao, Ki Hok

AU - Chen, Pei Hsing

AU - Huang, Pei Rong

AU - Huang, Sin Ming

AU - Lin, Tai Ching

AU - Lai, Wan Chun

AU - Chiu, Wei Tzu

AU - Chiang, Xu Heng

AU - Chang, Ya Ling

AU - Chen, Yan Ming

AU - Chen, Yi Ling

AU - Wang, Yi Wen

AU - Lin, Yi Wei

AU - Chang, Yu Cheng

AU - Huang, Yu Ting

AU - Lien, Yuju

AU - Zheng, Zhe Rong

AU - Hashimi, Abdul Samad

AU - Mohan, Adrij

AU - Pandey, Akhilesh

AU - Pilozzi, Alexander

AU - Webster, Alex

AU - Paulovich, Amanda G.

AU - Dagar, Aniket

AU - Godwin, Andrew K.

AU - Pruetz, Barbara

AU - Williams, Bart O.

AU - Druker, Brian J.

AU - Rohrer, Daniel C.

AU - Chan, Daniel W.

AU - Petrov, Danail

AU - Chesla, David

AU - Davaar, Diwakar

AU - Duffy, Elizabeth

AU - Wilson, George D.

AU - Zhao, Grace

AU - Kołodziejczak, Iga

AU - Lubinski, Jan

AU - Huang, Jasmine

AU - Hafron, Jason

AU - Tyner, Jeffrey W.

AU - Koomen, John

AU - Zaalishvili, Kakhaber

AU - Ketchum, Karen A.

AU - Wiznerowicz, Maciej

AU - Domagalski, Marcin J.

AU - Anurag, Meenakshi

AU - Borucki, Melissa

AU - Edwards, Nathan J.

AU - Vatanian, Negin

AU - Grady, Pamela

AU - Piehowski, Paul D.

AU - Bogdan, Popovici

AU - Li, Qin

AU - Fonseca, Rafael

AU - Madan, Rashna

AU - Thangudu, Ratna R.

AU - Crispen, Reese

AU - Matteotti, Ronald

AU - Bremner, Ross

AU - Cerda, Sandra

AU - Cottingham, Sandra L.

AU - Tsang, Shirley

AU - Cai, Shuang

AU - Liu, Tao

AU - Bauer, Thomas

AU - Maggio, William W.

AU - Jing, Xiaojun

AU - Zhang, Yuping

AU - Shutack, Yvonne

AU - Andric, Zoran

PY - 2025/9/8

Y1 - 2025/9/8

N2 - 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.

AB - 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.

KW - CPTAC

KW - ICPC

KW - PTMs

KW - biomarkers

KW - genomics

KW - lung adenocarcinoma

KW - mass spectrometry

KW - never-smokers

KW - proteogenomics

KW - smokers

UR - https://www.scopus.com/pages/publications/105012537751

U2 - 10.1016/j.ccell.2025.07.011

DO - 10.1016/j.ccell.2025.07.011

M3 - Article

C2 - 40749670

AN - SCOPUS:105012537751

SN - 1535-6108

VL - 43

SP - 1731-1757.e17

JO - Cancer Cell

JF - Cancer Cell

IS - 9

ER -

Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures

Abstract

UN SDGs

Keywords

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