Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer
Xue Li,
Nai-Ren Zheng,
Lin-Heng Wang,
Zhong-Wu Li,
Zong-Chao Liu,
Hua Fan,
Yi Wang,
Jin Dai,
Xiao-Tian Ni,
Xin Wei,
Ming-Wei Liu,
Kai Li,
Zhe-Xuan Li,
Tong Zhou,
Yang Zhang,
Jing-Ying Zhang,
Gaohaer Kadeerhan,
Sha Huang,
Wen-Hui Wu,
Wei-Dong Liu,
Xiu-Zhen Wu,
Lan-Fu Zhang,
Jian-Ming Xu,
Markus Gerhard,
Wei-Cheng You,
Kai-Feng Pan,
Wen-Qing Li,
Jun Qin
Affiliations
Xue Li
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Nai-Ren Zheng
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
Lin-Heng Wang
Department of Gastroenterology, Second Clinical Medical College of Beijing University of Chinese Medicine (Dongfang Hospital), Beijing 100078, China
Zhong-Wu Li
Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Zong-Chao Liu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Hua Fan
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Yi Wang
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
Jin Dai
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Xiao-Tian Ni
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
Xin Wei
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
Ming-Wei Liu
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
Kai Li
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
Zhe-Xuan Li
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Tong Zhou
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Yang Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Jing-Ying Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Gaohaer Kadeerhan
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Sha Huang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Wen-Hui Wu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Wei-Dong Liu
Linqu County Public Health Bureau, Shandong 262600, China
Xiu-Zhen Wu
Linqu County People's Hospital, Shandong 262600, China
Lan-Fu Zhang
Linqu County People's Hospital, Shandong 262600, China
Jian-Ming Xu
Department of Gastrointestinal Oncology, The Fifth Medical Center, General Hospital of PLA, Beijing 100071, China
Markus Gerhard
PYLOTUM Key joint laboratory for upper GI cancer, Technische Universität München/Peking University Cancer Hospital & Institute, Munich/Beijing, Germany/ China
Wei-Cheng You
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China; PYLOTUM Key joint laboratory for upper GI cancer, Technische Universität München/Peking University Cancer Hospital & Institute, Munich/Beijing, Germany/ China
Kai-Feng Pan
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China; PYLOTUM Key joint laboratory for upper GI cancer, Technische Universität München/Peking University Cancer Hospital & Institute, Munich/Beijing, Germany/ China
Wen-Qing Li
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China; PYLOTUM Key joint laboratory for upper GI cancer, Technische Universität München/Peking University Cancer Hospital & Institute, Munich/Beijing, Germany/ China; Corresponding author.
Jun Qin
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280–473 days), and an independent case-control study from Beijing (n = 99). Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78–0.99) vs. 0.56 (0.36–0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins. Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention. Funding: The funders are listed in the Acknowledgement.
