標題: Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression
作者: 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
交大名義發表
National Chiao Tung University
公開日期: 9-Jul-2020
摘要: 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.
URI: http://dx.doi.org/10.1016/j.cell.2020.06.012
http://hdl.handle.net/11536/154899
ISSN: 0092-8674
DOI: 10.1016/j.cell.2020.06.012
期刊: CELL
Volume: 182
Issue: 1
起始頁: 226
結束頁: 0
Appears in Collections:Articles