Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

作者：Michael A. Gillette, Shankha Satpathy, Song Cao, Saravana Mohan Dhanasekaran, Suhas V. Vasaikar, Karsten Krug, Francesca Petralia, Yize Li, Wen-Wei Liang, Boris A. Reva, Azra Krek, Jiayi Ji, Xiaoyu Song, Wenke Liu, Runyu Hong, Lijun Yao, Lili M. Blumenberg, Sara R. Savage, Michael C. Wendl, Bo Wen, Kai Li, Lauren C. Tang, Melanie A. MacMullan, Shayan C. Avanessian, M. Harry Kane, Chelsea J. Newton, MacIntosh Cornwell, Ramani Bhupendra Kothadia, Weiping Ma, Seungyeul Yoo, Rahul Mannan, Pankaj Vats, Chandan Kumar‐Sinha, Emily A. Kawaler, Tatiana Omelchenko, Antonio Colaprico, Yifat Geffen, Yosef E. Maruvka, Felipe da Veiga Leprevost, Maciej Wiznerowicz, Zeynep Hulya Gumus, Rajwanth R. Veluswamy, Galen H. Hostetter, David I. Heiman, Matthew A. Wyczalkowski, Tara Hiltke, Mehdi Mesri, Christopher R. Kinsinger, Emily S. Boja, Gilbert S. Omenn, Arul M. Chinnaiyan, Henry Rodriguez, Qing Kay Li, Scott D. Jewell, Mathangi Thiagarajan, Gad A. Getz, Bing Zhang, David Fenyö, Kelly V. Ruggles, Marcin P. Cieslik, Ana I. Robles, Karl R. Clauser, Ramaswamy Govindan, Pei Wang, Alexey I. Nesvizhskii, Li Ding, D.R. Mani, Steven A. Carr, Alex Webster, Alicia Francis, Alyssa Charamut, Amanda G. Paulovich, Amy M. Perou, Andrew K. Godwin, Andrii Karnuta, Annette Marrero-Oliveras, Barbara Hindenach, Barbara L. Pruetz, Bartosz Kubisa, Brian Druker, Chet Birger, Corbin D. Jones, Dana R. Valley, Daniel C. Rohrer, Daniel Cui Zhou, Daniel W. Chan, David W. Chesla, David J. Clark, Dmitry Rykunov, Donghui Tan, Elena V. Ponomareva, Elizabeth R. Duffy, Eric Burks, Eric E. Schadt, Erik J. Bergstrom, Eugene Fedorov, Ewa P. Malc, George David Wilson, Haiquan Chen, Halina M. Krzystek, Hongwei Liu, Houston Culpepper, Hua Sun, Hui Zhang, Jacob Oliver Day, James H. Suh, Jeffrey R. Whiteaker, Jennifer Eschbacher, John P. McGee, Karen A. Ketchum, Karin Rodland, Karna Robinson, Katherine A. Hoadley, Kei Suzuki, Ki Sung Um, Kim Elburn, Liang-Bo Wang, Lijun Chen, Linda I. Hannick, Liqun Qi, Lori J. Sokoll, Małgorzata Edyta Wojtyś, Marcin Jakub Domagalski, Marina A. Gritsenko, Mary Beth Beasley, Matthew E Monroe, Matthew J. Ellis, Maureen A. Dyer, Meghan C. Burke, Melissa Borucki, Menghong Sun, Michael H. A. Roehrl, Michael J. Birrer, Michael S. Noble, Michael Schnaubelt, Michael W. Vernon, Michelle Chaikin, Mikhail Krotevich, Munziba Khan, Myvizhi Esai Selvan, Nancy Roche, Nathan J Edwards, Negin Vatanian, Olga Potapova, Pamela Grady, Peter B. McGarvey, Piotr A. Mieczkowski, Pushpa Hariharan, Rashna Madan, Ratna Rajesh Thangudu, Richard Smith, Robert Welsh, Robert Zelt, Rohit S Mehra, Ronald Matteotti, Sailaja Mareedu, Samuel Payne, Sandra L. Cottingham, Sanford P. Markey, Seema Chugh, Shaleigh A. Smith, Shirley X. Tsang, Shuang Cai, Simina Maria Boca, Sonya Carter, Stacey L. Gabriel, Stephanie Young, Stephen E. Stein, Sunita Shankar, Tanya Krubit, Tao Liu, Tara J. Skelly, THOMAS L BAUER, Uma Velvulou, Umut Özbek, Vladislav Petyuk, Volodymyr Sovenko, William Bocik, William W. Maggio, Xi Chen, Yan Shi, Yige Wu, Yingwei Hu, Yuxing Liao, Zhen Zhang, Zhiao Shi · 发表于：Cell · 年份：2020 · DOI：10.1016/j.cell.2020.06.013 · 被引用次数：862 · 研究领域：RNA modifications and cancer、Ferroptosis and cancer prognosis、Lung Cancer Treatments and Mutations

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.