Proteogenomic landscape of squamous cell lung cancer.

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.

• Authors: 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, Eric B Haura
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 3578 (08 08 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31395880 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Aged
• Carcinoma, Squamous Cell (genetics, pathology)
• DNA Copy Number Variations
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung
• Lung Neoplasms (genetics, pathology)
• Male
• Middle Aged
• Mutation
• Proteogenomics
• Sequence Analysis, RNA