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Nat Commun. 2019 Aug 8;10(1):3578. doi: 10.1038/s41467-019-11452-x.

Proteogenomic landscape of squamous cell lung cancer.

Author information

1
Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
2
Biostatistics and Bioinformatics Shared Resource, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
3
Proteomics Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
4
Department of Anatomical Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
5
Molecular Genomics Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
6
Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
7
Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
8
Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
9
Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
10
Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA. eric.haura@moffitt.org.

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.

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