Chen, Yi-JuYi-JuChenRoumeliotis, Theodoros ITheodoros IRoumeliotisChang, Ya-HsuanYa-HsuanChangChen, Ching-TaiChing-TaiChenHan, Chia-LiChia-LiHanMIAO-HSIA LINHUEI-WEN CHENChang, Gee-ChenGee-ChenChangYIH-LEONG CHANGCHEN-TU WUMONG-WEI LINMIN-SHU HSIEHWang, Yu-TaiYu-TaiWangChen, Yet-RanYet-RanChenJonassen, IngeIngeJonassenGhavidel, Fatemeh ZamanzadFatemeh ZamanzadGhavidelLin, Ze-ShiangZe-ShiangLinLin, Kuen-TyngKuen-TyngLinChen, Ching-WenChing-WenChenSheu, Pei-YuanPei-YuanSheuHung, Chen-TingChen-TingHungHuang, Ke-ChiehKe-ChiehHuangYang, Hao-ChinHao-ChinYangLin, Pei-YiPei-YiLinYen, Ta-ChiTa-ChiYenLin, Yi-WeiYi-WeiLinWang, Jen-HungJen-HungWangRaghav, LovelyLovelyRaghavLin, Chien-YuChien-YuLinChen, Yan-SiYan-SiChenWu, Pei-ShanPei-ShanWuLai, Chi-TingChi-TingLaiWeng, Shao-HsingShao-HsingWengKANG-YI SUChang, Wei-HungWei-HungChangTsai, Pang-YanPang-YanTsaiRobles, Ana IAna IRoblesRodriguez, HenryHenryRodriguezHsiao, Yi-JingYi-JingHsiaoChang, Wen-HsinWen-HsinChangSung, Ting-YiTing-YiSungJIN-SHING CHENSUNG-LIANG YUChoudhary, Jyoti SJyoti SChoudharyChen, Hsuan-YuHsuan-YuChenPAN-CHYR YANGChen, Yu-JuYu-JuChen2020-12-022020-12-0220200092-8674https://www.scopus.com/inward/record.uri?eid=2-s2.0-85087414083&doi=10.1016%2fj.cell.2020.06.012&partnerID=40&md5=44230bf3133af3dd0917919994fd4150https://scholars.lib.ntu.edu.tw/handle/123456789/523424Deep 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]SDG3adult; 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; Smokingjournal article10.1016/j.cell.2020.06.012326498752-s2.0-85087414083