1. Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.
- Author
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Chen YJ, Roumeliotis TI, Chang YH, Chen CT, Han CL, Lin MH, Chen HW, Chang GC, Chang YL, Wu CT, Lin MW, Hsieh MS, Wang YT, Chen YR, Jonassen I, Ghavidel FZ, Lin ZS, Lin KT, Chen CW, Sheu PY, Hung CT, Huang KC, Yang HC, Lin PY, Yen TC, Lin YW, Wang JH, Raghav L, Lin CY, Chen YS, Wu PS, Lai CT, Weng SH, Su KY, Chang WH, Tsai PY, Robles AI, Rodriguez H, Hsiao YJ, Chang WH, Sung TY, Chen JS, Yu SL, Choudhary JS, Chen HY, Yang PC, and Chen YJ
- Subjects
- Adenocarcinoma of Lung genetics, Adenocarcinoma of Lung pathology, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Carcinogens toxicity, Cohort Studies, Cytosine Deaminase metabolism, Asia, Eastern, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genome, Human, Humans, Matrix Metalloproteinases metabolism, Mutation genetics, Principal Component Analysis, Disease Progression, Lung Neoplasms genetics, Lung Neoplasms pathology, Proteogenomics, Smoking genetics
- Abstract
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., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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