期刊
CELL
卷 182, 期 1, 页码 226-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.06.012
关键词
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资金
- Next-Generation Pathway of Taiwan Cancer Precision Medicine Program [AS-KPQ-107-TCPMP]
- Taiwan Protein Project at Academia Sinica [AS-KPQ-105-TPP]
- Ministry of Science and Technology [MOST-106-3114-Y-043F-014, MOST108-2319-B-002-001, MOST 107-0210-01-19-01, MOST 108-3114-Y-001-002]
- National Taiwan University in Taiwan [NTU-CDP-106R7891]
- Academia Sinica Common Mass Spectrometry Facilities [AS-CFII-108-107]
- National Core Facility for Biopharmaceuticals Pharmacogenomics Lab TR6 [MOST108-2319-B-002-001]
- National Center for High-Performance Computing of National Applied Research Laboratories in Taiwan [MOST 108-2319B-492-001]
- Center of Precision Medicine from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE), Taiwan
- CRUK Centre, UK [C309/A25144]
- Academia Sinica
- U.S. National Cancer Institute's International Cancer Proteogenome Consortium (ICPC)
Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.
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