. 2020 Jul 9;182(1):245-261.e17.

doi: 10.1016/j.cell.2020.05.043.

Integrative Proteomic Characterization of Human Lung Adenocarcinoma

Jun-Yu Xu¹, Chunchao Zhang², Xiang Wang³, Linhui Zhai¹, Yiming Ma⁴, Yousheng Mao⁵, Kun Qian⁶, Changqing Sun⁷, Zhiwei Liu⁸, Shangwen Jiang¹, Minghui Wang³, Lin Feng³, Lei Zhao¹, Ping Liu¹, Bo Wang⁴, Xin Zhao⁶, Hui Xie⁷, Xiaoyun Yang⁴, Liyuan Zhao⁴, Yafei Chang⁴, Jingya Jia⁴, Xijun Wang³, Yimin Zhang⁴, Yaru Wang³, Yikun Yang⁵, Zhixiang Wu¹, Longhai Yang⁵, Bin Liu¹, Teng Zhao⁶, Shengguo Ren⁹, Aihua Sun², Yang Zhao², Wantao Ying², Fei Wang⁹, Guangshun Wang¹⁰, Yi Zhang⁶, Shujun Cheng³, Jun Qin², Xiaohong Qian², Yi Wang¹¹, Jing Li¹², Fuchu He¹³, Ting Xiao¹⁴, Minjia Tan¹⁵

Affiliations

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
² State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
³ State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
⁴ Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
⁵ Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
⁶ Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
⁷ Department of Oncology, Tianjin Baodi Hospital, Tianjin 301800, China.
⁸ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of the Chinese Academy of Sciences, Beijing, China.
⁹ Shanghai Key Laboratory of Intelligent Information Processing, School of Computer Science and Technology, Fudan University, Shanghai 200433, China.
¹⁰ Department of Oncology, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, China.
¹¹ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address: wangyi@ncpsb.org.cn.
¹² Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: jing.li@sjtu.edu.cn.
¹³ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address: hefc@nic.bmi.ac.cn.
¹⁴ State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: xiaot@cicams.ac.cn.
¹⁵ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of the Chinese Academy of Sciences, Beijing, China. Electronic address: mjtan@simm.ac.cn.

PMID: 32649877
DOI: 10.1016/j.cell.2020.05.043

Free article

Integrative Proteomic Characterization of Human Lung Adenocarcinoma

Jun-Yu Xu et al. Cell. 2020.

Free article

. 2020 Jul 9;182(1):245-261.e17.

doi: 10.1016/j.cell.2020.05.043.

Authors

Affiliations

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
² State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
³ State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
⁴ Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
⁵ Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
⁶ Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
⁷ Department of Oncology, Tianjin Baodi Hospital, Tianjin 301800, China.
⁸ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of the Chinese Academy of Sciences, Beijing, China.
⁹ Shanghai Key Laboratory of Intelligent Information Processing, School of Computer Science and Technology, Fudan University, Shanghai 200433, China.
¹⁰ Department of Oncology, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, China.
¹¹ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address: wangyi@ncpsb.org.cn.
¹² Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: jing.li@sjtu.edu.cn.
¹³ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address: hefc@nic.bmi.ac.cn.
¹⁴ State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: xiaot@cicams.ac.cn.
¹⁵ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of the Chinese Academy of Sciences, Beijing, China. Electronic address: mjtan@simm.ac.cn.

PMID: 32649877
DOI: 10.1016/j.cell.2020.05.043

Abstract

Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD remain poorly understood. We carried out a comprehensive proteomics analysis of 103 cases of LUAD in Chinese patients. Integrative analysis of proteome, phosphoproteome, transcriptome, and whole-exome sequencing data revealed cancer-associated characteristics, such as tumor-associated protein variants, distinct proteomics features, and clinical outcomes in patients at an early stage or with EGFR and TP53 mutations. Proteome-based stratification of LUAD revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Further, we nominated potential drug targets and validated the plasma protein level of HSP 90β as a potential prognostic biomarker for LUAD in an independent cohort. Our integrative proteomics analysis enables a more comprehensive understanding of the molecular landscape of LUAD and offers an opportunity for more precise diagnosis and treatment.

Keywords: biomarker; clinical outcome; drug target; genomics; lung adenocarcinoma; mass spectrometry; phosphoproteomics; precision medicine; proteomics; regulatory network.

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Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

Comment in

Across the Globe: Proteogenomic Landscapes of Lung Cancer.
Yanovich-Arad G, Geiger T. Yanovich-Arad G, et al. Cell. 2020 Jul 9;182(1):9-11. doi: 10.1016/j.cell.2020.06.016. Cell. 2020. PMID: 32649881
Proteogenomics reveals molecular subtypes.
Sidaway P. Sidaway P. Nat Rev Clin Oncol. 2020 Sep;17(9):519. doi: 10.1038/s41571-020-0419-6. Nat Rev Clin Oncol. 2020. PMID: 32719419 No abstract available.
Proteogenomics Clarifies Picture of Lung Cancer.
[No authors listed] [No authors listed] Cancer Discov. 2020 Oct;10(10):OF3. doi: 10.1158/2159-8290.CD-NB2020-071. Epub 2020 Aug 5. Cancer Discov. 2020. PMID: 32759305

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Integrative Proteomic Characterization of Human Lung Adenocarcinoma

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Integrative Proteomic Characterization of Human Lung Adenocarcinoma

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Abstract

Conflict of interest statement

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