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: | 9-七月-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 |
顯示於類別: | 期刊論文 |