Proteogenomic landscape of squamous cell lung cancer

Paul A. Stewart, Eric A. Welsh, Robbert J. C. Slebos, Bin Fang, Victoria Izumi, Matthew Chambers, Guolin Zhang, Ling Cen, Fredrik Pettersson, Yonghong Zhang, Zhihua Chen, Chia-Ho Cheng, Ram Thapa, Zachary Thompson, Katherine M. Fellows, Jewel M. Francis, James J. Saller, Tania Mesa, Chaomei Zhang, Sean Yoder, Gina M. DeNicola, Amer A. Beg, Theresa A. Boyle, Jamie K. Teer, Yian Ann Chen, John M. Koomen, Steven A. Eschrich and Eric B. Haura ()
Additional contact information
Paul A. Stewart: H. Lee Moffitt Cancer Center and Research Institute
Eric A. Welsh: H. Lee Moffitt Cancer Center and Research Institute
Robbert J. C. Slebos: H. Lee Moffitt Cancer Center and Research Institute
Bin Fang: H. Lee Moffitt Cancer Center and Research Institute
Victoria Izumi: H. Lee Moffitt Cancer Center and Research Institute
Matthew Chambers: H. Lee Moffitt Cancer Center and Research Institute
Guolin Zhang: H. Lee Moffitt Cancer Center and Research Institute
Ling Cen: H. Lee Moffitt Cancer Center and Research Institute
Fredrik Pettersson: H. Lee Moffitt Cancer Center and Research Institute
Yonghong Zhang: H. Lee Moffitt Cancer Center and Research Institute
Zhihua Chen: H. Lee Moffitt Cancer Center and Research Institute
Chia-Ho Cheng: H. Lee Moffitt Cancer Center and Research Institute
Ram Thapa: H. Lee Moffitt Cancer Center and Research Institute
Zachary Thompson: H. Lee Moffitt Cancer Center and Research Institute
Katherine M. Fellows: H. Lee Moffitt Cancer Center and Research Institute
Jewel M. Francis: H. Lee Moffitt Cancer Center and Research Institute
James J. Saller: H. Lee Moffitt Cancer Center and Research Institute
Tania Mesa: H. Lee Moffitt Cancer Center and Research Institute
Chaomei Zhang: H. Lee Moffitt Cancer Center and Research Institute
Sean Yoder: H. Lee Moffitt Cancer Center and Research Institute
Gina M. DeNicola: H. Lee Moffitt Cancer Center and Research Institute
Amer A. Beg: H. Lee Moffitt Cancer Center and Research Institute
Theresa A. Boyle: H. Lee Moffitt Cancer Center and Research Institute
Jamie K. Teer: H. Lee Moffitt Cancer Center and Research Institute
Yian Ann Chen: H. Lee Moffitt Cancer Center and Research Institute
John M. Koomen: H. Lee Moffitt Cancer Center and Research Institute
Steven A. Eschrich: H. Lee Moffitt Cancer Center and Research Institute
Eric B. Haura: H. Lee Moffitt Cancer Center and Research Institute

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract How genomic and transcriptomic alterations affect the functional proteome in lung cancer is not fully understood. Here, we integrate DNA copy number, somatic mutations, RNA-sequencing, and expression proteomics in a cohort of 108 squamous cell lung cancer (SCC) patients. We identify three proteomic subtypes, two of which (Inflamed, Redox) comprise 87% of tumors. The Inflamed subtype is enriched with neutrophils, B-cells, and monocytes and expresses more PD-1. Redox tumours are enriched for oxidation-reduction and glutathione pathways and harbor more NFE2L2/KEAP1 alterations and copy gain in the 3q2 locus. Proteomic subtypes are not associated with patient survival. However, B-cell-rich tertiary lymph node structures, more common in Inflamed, are associated with better survival. We identify metabolic vulnerabilities (TP63, PSAT1, and TFRC) in Redox. Our work provides a powerful resource for lung SCC biology and suggests therapeutic opportunities based on redox metabolism and immune cell infiltrates.

Date: 2019
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DOI: 10.1038/s41467-019-11452-x

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