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Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.
Chen, Yi-Ju; Roumeliotis, Theodoros I; Chang, Ya-Hsuan; Chen, Ching-Tai; Han, Chia-Li; Lin, Miao-Hsia; Chen, Huei-Wen; Chang, Gee-Chen; Chang, Yih-Leong; Wu, Chen-Tu; Lin, Mong-Wei; Hsieh, Min-Shu; 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; Su, Kang-Yi; Chang, Wei-Hung; Tsai, Pang-Yan; Robles, Ana I; Rodriguez, Henry; Hsiao, Yi-Jing; Chang, Wen-Hsin; Sung, Ting-Yi; Chen, Jin-Shing; Yu, Sung-Liang; Choudhary, Jyoti S; Chen, Hsuan-Yu; Yang, Pan-Chyr; Chen, Yu-Ju.
Afiliação
  • Chen YJ; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Roumeliotis TI; Functional Proteomics Group, Chester Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB, UK.
  • Chang YH; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
  • Chen CT; Institute of Information Science, Academia Sinica, Taipei, Taiwan.
  • Han CL; Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: was@tmu.edu.tw.
  • Lin MH; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Chen HW; Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Chang GC; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
  • Chang YL; Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
  • Wu CT; Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
  • Lin MW; Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
  • Hsieh MS; Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
  • Wang YT; National Applied Research Laboratories, National Center for High-performance Computing, Hsinchu, Taiwan.
  • Chen YR; Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
  • Jonassen I; Computational Biology Unit (CBU), Informatics Department, University of Bergen, Bergen, Norway.
  • Ghavidel FZ; Computational Biology Unit (CBU), Informatics Department, University of Bergen, Bergen, Norway.
  • Lin ZS; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Lin KT; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Chen CW; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Sheu PY; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Hung CT; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Huang KC; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Yang HC; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Lin PY; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Yen TC; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Lin YW; Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
  • Wang JH; Institute of Information Science, Academia Sinica, Taipei, Taiwan.
  • Raghav L; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan; Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Bioinformatics Program, Taiwan International Graduate Program, Hsinchu, Taiwan.
  • Lin CY; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
  • Chen YS; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
  • Wu PS; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Lai CT; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Weng SH; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Su KY; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Chang WH; Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
  • Tsai PY; Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
  • Robles AI; Office of Cancer Clinical Proteomics Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Rodriguez H; Office of Cancer Clinical Proteomics Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Hsiao YJ; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Chang WH; Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
  • Sung TY; Institute of Information Science, Academia Sinica, Taipei, Taiwan. Electronic address: tsung@iis.sinica.edu.tw.
  • Chen JS; Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: chenjs@ntu.edu.tw.
  • Yu SL; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: slyu@ntu.edu.tw.
  • Choudhary JS; Functional Proteomics Group, Chester Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB, UK. Electronic address: jyoti.choudhary@icr.ac.uk.
  • Chen HY; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan; Ph.D. Program in Microbial Genomics, National Chung Hsing University, Taichung, Taiwan. Electronic address: hychen@stat.sinica.edu.tw.
  • Yang PC; Department of Internal Medicine, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address: pcyang@ntu.edu.tw.
  • Chen YJ; Institute of Chemistry, Academia Sinica, Taipei, Taiwan; Department of Chemistry, National Taiwan University, Taipei, Taiwan. Electronic address: yujuchen@gate.sinica.edu.tw.
Cell ; 182(1): 226-244.e17, 2020 07 09.
Article em En | MEDLINE | ID: mdl-32649875
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fumar / Progressão da Doença / Proteogenômica / Neoplasias Pulmonares Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Humans País como assunto: Asia Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fumar / Progressão da Doença / Proteogenômica / Neoplasias Pulmonares Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Humans País como assunto: Asia Idioma: En Ano de publicação: 2020 Tipo de documento: Article