Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma.

Cell
Authors
Keywords
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.

Year of Publication
2020
Journal
Cell
Volume
182
Issue
1
Pages
200-225.e35
Date Published
2020 07 09
ISSN
1097-4172
DOI
10.1016/j.cell.2020.06.013
PubMed ID
32649874
PubMed Central ID
PMC7373300
Links
Grant list
U24 CA210954 / CA / NCI NIH HHS / United States
U24 CA210967 / CA / NCI NIH HHS / United States
U24 CA210986 / CA / NCI NIH HHS / United States
U24 CA210972 / CA / NCI NIH HHS / United States
P20 GM130423 / GM / NIGMS NIH HHS / United States
P30 ES017885 / ES / NIEHS NIH HHS / United States
U24 CA210993 / CA / NCI NIH HHS / United States
U24 CA210979 / CA / NCI NIH HHS / United States
U01 CA214125 / CA / NCI NIH HHS / United States