Dataset Information

Proteogenomic Landscape of Squamous Cell Lung Cancer 1: Digestion QC with DIA LC-MS/MS

ABSTRACT: We report an integrated analysis incorporating DNA copy number analyses, somatic exon mutations, mRNA expression via RNA-sequencing, and shotgun mass spectrometry analysis of protein abundance in 108 surgically resected squamous cell lung cancers (SCC) with accompanying clinical outcome, evaluation of tumor pathology, and other clinically relevant data. We identified three major subtypes of SCC at the proteomic level, with two groups associated with inflammation/immune response or oxidation-reduction biology. Inflamed tumors could be further sub-classified based on neutrophil infiltration or antigen presentation proteomes and reflected patterns of infiltrating immune cells. No gene mutations, mRNA signatures, or proteomic subclasses were associated with outcomes; however, the presence of B-cell rich tertiary lymph node structures could be associated with better patient outcomes. By integrating our proteogenomic data with publicly available RNA interference screen data, we identified TP63, PSAT1, and AKR1C3 as vulnerabilities in SCC, particularly in the redox proteomic group. This cohort and its deep molecular data serves as an important resource to better understand biology and targets associated with SCC.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

DISEASE(S): Non-small Cell Lung Carcinoma

SUBMITTER: John Koomen

LAB HEAD: Eric Haura, MD

PROVIDER: PXD010357 | Pride | 2019-05-24

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20160301_Haura-SCC-PG-06S15092277-DIA.raw	Raw
	20160301_Haura-SCC-PG-06S15092277-DIA.raw (F005831).mzid_20160301_Haura-SCC-PG-06S15092277-DIA.raw_(F005831).pride.mgf.gz	Mzid
	20160301_Haura-SCC-PG-06S15092277-DIA.rawF005831.mzid.gz	Mzid
	20160301_Haura-SCC-PG-06S15092277-DIA.rawF005831.mzid_20160301_Haura-SCC-PG-06S15092277-DIA.raw_F005831.MGF	Mzid
	20160301_Haura-SCC-PG-06S15092277-DIA.raw_(F005831).pride.mgf.gz	Mgf

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Publications

Proteogenomic landscape of squamous cell lung cancer.

Stewart Paul A PA Welsh Eric A EA Slebos Robbert J C RJC Fang Bin B Izumi Victoria V Chambers Matthew M Zhang Guolin G Cen Ling L Pettersson Fredrik F Zhang Yonghong Y Chen Zhihua Z Cheng Chia-Ho CH Thapa Ram R Thompson Zachary Z Fellows Katherine M KM Francis Jewel M JM Saller James J JJ Mesa Tania T Zhang Chaomei C Yoder Sean S DeNicola Gina M GM Beg Amer A AA Boyle Theresa A TA Teer Jamie K JK Ann Chen Yian Y Koomen John M JM Eschrich Steven A SA Haura Eric B EB

Nature communications 20190808 1

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 oxida ...[more]

PMID: 31395880

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