Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression
Journal
Cell
Journal Volume
182
Journal Issue
1
Pages
226-244.e17
Date Issued
2020
Author(s)
Chen, Yi-Ju
Roumeliotis, Theodoros I
Chang, Ya-Hsuan
Chen, Ching-Tai
Han, Chia-Li
Chang, Gee-Chen
Wang, Yu-Tai
Chen, Yet-Ran
Jonassen, Inge
Ghavidel, Fatemeh Zamanzad
Lin, Ze-Shiang
Lin, Kuen-Tyng
Chen, Ching-Wen
Sheu, Pei-Yuan
Hung, Chen-Ting
Huang, Ke-Chieh
Yang, Hao-Chin
Lin, Pei-Yi
Yen, Ta-Chi
Lin, Yi-Wei
Wang, Jen-Hung
Raghav, Lovely
Lin, Chien-Yu
Chen, Yan-Si
Wu, Pei-Shan
Lai, Chi-Ting
Weng, Shao-Hsing
Chang, Wei-Hung
Tsai, Pang-Yan
Robles, Ana I
Rodriguez, Henry
Hsiao, Yi-Jing
Chang, Wen-Hsin
Sung, Ting-Yi
Choudhary, Jyoti S
Chen, Hsuan-Yu
Chen, Yu-Ju
Abstract
Deep proteogenomic landscape of early stage lung adenocarcinoma in a cohort of mostly non-smokers reveals unique drivers and biomarkers, as well as gender-associated mutagenesis. ? 2020 Elsevier Inc.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. ? 2020 Elsevier Inc.
SDGs
Other Subjects
adult; Article; cancer classification; cancer growth; cancer staging; cohort analysis; controlled study; demography; EGFR gene; female; gender; gene; gene mutation; genetic analysis; genomics; groups by age; health care need; human; human tissue; lung adenocarcinoma; lung cancer; major clinical study; male; middle aged; mutagenesis; pathogenesis; phosphoproteomics; prevalence; priority journal; protein analysis; protein phosphorylation; proteogenomics; Taiwan; Taiwanese; disease exacerbation; Far East; gene expression regulation; gene regulatory network; genetics; human genome; lung tumor; metabolism; mutation; pathology; principal component analysis; smoking; carcinogen; cytosine deaminase; matrix metalloproteinase; tumor marker; Adenocarcinoma of Lung; Biomarkers, Tumor; Carcinogens; Cohort Studies; Cytosine Deaminase; Disease Progression; Far East; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genome, Human; Humans; Lung Neoplasms; Matrix Metalloproteinases; Mutation; Principal Component Analysis; Proteogenomics; Smoking
Publisher
Cell Press
Type
journal article