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Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Authors
Michael Gillette,Shankha Satpathy
Song Cao,Saravana Dhanasekaran,Suhas Vasaikar,Karsten Krug,Francesca Petralia,Yize Li,Wen-Wei Liang,Boris Reva,Azra Krek,Jiayi Ji,Xiaoyu Song,Wenke Liu,Runyu Hong,Tomer Yaron,Lili Blumenberg,Sara Savage,Michael Wendl,Bo Wen,Kai Li,Lauren Tang,Melanie MacMullan,Shayan Avanessian,M. Kane,Chelsea Newton,MacIntosh Cornwell,Ramani Kothadia,Weiping Ma,Seungyeul Yoo,Rahul Mannan,Pankaj Vats,Chandan Kumar‐Sinha,Emily Kawaler,Tatiana Omelchenko,Antonio Colaprico,Yifat Geffen,Yosef Maruvka,Felipe Leprevost,Maciej Wiznerowicz,Zeynep Gümüş,Rajwanth Veluswamy,Galen Hostetter,David Heiman,Matthew Wyczalkowski,Tara Hiltke,Mehdi Mesri,Christopher Kinsinger,Emily Boja,Gilbert Omenn,Arul Chinnaiyan,Henry Rodriguez,Qing Li,Scott Jewell,Mathangi Thiagarajan,Gad Getz,Bing Zhang,David Fenyö,Kelly Ruggles,Marcin Cieślik,Ana Robles,Karl Clauser,Ramaswamy Govindan,Pei Wang,Alexey Nesvizhskii,Li Ding,D.R. Mani,Steven Carr,Alex Webster,Alicia Francis,Alyssa Charamut,Amanda Paulovich,Amy Perou,Andrew Godwin,Andrii Karnuta,Annette Marrero-Oliveras,Barbara Hindenach,Barbara Pruetz,Bartosz Kubisa,Brian Druker,Chet Birger,Corbin Jones,Dana Valley,Daniel Rohrer,Daniel Zhou,Daniel Chan,David Chesla,David Clark,Dmitry Rykunov,Donghui Tan,Elena Ponomareva,Elizabeth Duffy,Eric Burks,Eric Schadt,Erik Bergstrom,Eugene Fedorov,Ewa Malc,George Wilson,Haiquan Chen,Halina Krzystek,Hongwei Liu,Houston Culpepper,Hua Sun,Hui Zhang,Jacob Day,James Suh,Jeffrey Whiteaker,Fu‐Dong Shi,John McGee,Karen Ketchum,Karin Rodland,Karna Robinson,Katherine Hoadley,Kei Suzuki,Ki Um,Kim Elburn,Liang-Bo Wang,Lijun Chen,Linda Hannick,Liqun Qi,Lori Sokoll,Małgorzata Wojtyś,Marcin Domagalski,Marina Gritsenko,Mary Beasley,Matthew Monroe,Matthew Ellis,Maureen Dyer,Meghan Burke,Melissa Borucki,Menghong Sun,Michael Roehrl,Michael Birrer,Michael Noble,Michael Schnaubelt,Michael Vernon,Michelle Chaikin,Mikhail Krotevich,Munziba Khan,Myvizhi Selvan,Nancy Roche,Nathan Edwards,Negin Vatanian,Olga Potapova,Pamela Grady,Peter McGarvey,Piotr Mieczkowski,Pushpa Hariharan,Rashna Madan,Ratna Thangudu,Richard Smith,Robert Welsh,Robert Zelt,Rohit Mehra,Ronald Matteotti,Sailaja Mareedu,Samuel Payne,Sandra Cottingham,Sanford Markey,Seema Chugh,Shaleigh Smith,Shirley Tsang,Shuang Cai,Simina Boca,Sonya Carter,Stacey Gabriel,Stephanie Young,Stephen Stein,Tanya Krubit,Tao Liu,Tara Skelly,Thomas Bauer,Uma Velvulou,Umut Özbek,Vladislav Petyuk,Volodymyr Sovenko,William Bocik,William Maggio,Xi Chen,Yan Shi,Yige Wu,Yingwei Hu,Yuxing Liao,Zhen Zhang,Zhiao Shi
+183 authors
,D. Mani
Journal
Published
Jul 1, 2020
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Abstract

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.

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