Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures

作者：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, J. Allen, Shayan C. Avanessian, M. Harry Kane, A. Wolfe, Miloni Kinarivala, Wenke Liu, Shankara Anand, Mong‐Wei Lin, Moe Haines, Erik J. Bergstrom, Grant Hussey, Ginny Xiaohe Li, Deepak 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, R E Espinoza, Ma Weiping, Daniel Charytonowicz, Robert Sebra, Jyun-Hong Lin, Yan-Si Chen, Yin-Chen Hsu, Ze‐Shiang Lin, Kun-Chieh Chen, Chang‐Wei Yeh, Yutai Wang, Alexander J. Lazar, Mehdi Mesri, Eunkyung An, Xu Zhang, Karl R. Clauser, David Fenyö, Arul M. Chinnaiyan, Bing Zhang, Li Ding, Kelly V. Ruggles, Chelsea J. Newton, Hui Zhang, Pei Wang, Galen Hostetter, Gilbert S. Omenn, Chandan Kumar‐Sinha, Mathangi Thiagarajan, Ramaswamy Govindan, Paul K. Paik, Abhijit Parolia, Qing K. Li, Avi Ma’ayan, Gad 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 Cieślik, 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, Jingwei Lin, Juani Waniwan, Ki-Hok Liao, Pei‐Hsing Chen, Peirong 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, A. Samad Hashimi, Adrij Mohan, Akhilesh Pandey, Alexander Pilozzi, Alex Webster, Amanda G. Paulovich, Aniket Dagar, Andrew K. Godwin, Barbara L. Pruetz, Bart O. Williams, Brian Druker, Daniel C. Rohrer, Daniel W. Chan, Danail Petrov, David Chesla, Diwakar Davaar, Elizabeth R. Duffy, George D. Wilson, Grace Zhao, Iga Kołodziejczak, Jan Lubiński, Jasmine Huang, Jason Hafron, Jeffrey Tyner, John M. Koomen, Kakhaber Zaalishvili, Karen A. Ketchum, Maciej Wiznerowicz, Marcin J. Domagalski, Meenakshi Anurag, Melissa Borucki, Nathan Edwards, Negin Vatanian, Pamela Grady, Paul Piehowski, Popovici Bogdan, Qin Li, Rafaël Fonseca, Rashna Madan, Ratna R. Thangudu, Reese Crispen, Ronald Matteotti, Ross M. Bremner, Sandra Cerda, Sandra Cottingham, Shirley Tsang, Shuang Cai, Tao Liu, Thomas Bauer, William W. Maggio, Xiaojun Jing, Yuping Zhang, Yvonne Shutack, Zoran Andrić · 发表于：Cancer Cell · 年份：2025 · DOI：10.1016/j.ccell.2025.07.011 · 被引用次数：10 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、Lung Cancer Research Studies

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.