Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.
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Date
2020-07-09Author
Chen, Y-J
Roumeliotis, TI
Chang, Y-H
Chen, C-T
Han, C-L
Lin, M-H
Chen, H-W
Chang, G-C
Chang, Y-L
Wu, C-T
Lin, M-W
Hsieh, M-S
Wang, Y-T
Chen, Y-R
Jonassen, I
Ghavidel, FZ
Lin, Z-S
Lin, K-T
Chen, C-W
Sheu, P-Y
Hung, C-T
Huang, K-C
Yang, H-C
Lin, P-Y
Yen, T-C
Lin, Y-W
Wang, J-H
Raghav, L
Lin, C-Y
Chen, Y-S
Wu, P-S
Lai, C-T
Weng, S-H
Su, K-Y
Chang, W-H
Tsai, P-Y
Robles, AI
Rodriguez, H
Hsiao, Y-J
Chang, W-H
Sung, T-Y
Chen, J-S
Yu, S-L
Choudhary, JS
Chen, H-Y
Yang, P-C
Chen, Y-J
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Lung Neoplasms
Disease Progression
Cytosine Deaminase
Matrix Metalloproteinases
Carcinogens
Cohort Studies
Smoking
Gene Expression Regulation, Neoplastic
Mutation
Genome, Human
Principal Component Analysis
Far East
Gene Regulatory Networks
Biomarkers, Tumor
Proteogenomics
Adenocarcinoma of Lung
Language
eng
Date accepted
2020-06-03
License start date
2020-07
Citation
Cell, 2020, 182 (1), pp. 226 - 244.e17
Publisher
CELL PRESS
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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