title: Identification of Serum Biomarkers for Gastric Cancer Diagnosis Using a Human Proteome Microarray.
abstract: We aimed to globally discover serum biomarkers for diagnosis of gastric cancer (GC). GC serum autoantibodies were discovered and validated using serum samples from independent patient cohorts encompassing 1,401 participants divided into three groups, i.e. healthy, GC patients, and GC-related disease group. To discover biomarkers for GC, the human proteome microarray was first applied to screen specific autoantibodies in a total of 87 serum samples from GC patients and healthy controls. Potential biomarkers were identified via a statistical analysis protocol. Targeted protein microarrays with only the potential biomarkers were constructed and used to validate the candidate biomarkers using 914 samples. To provide further validation, the abundance of autoantibodies specific to the biomarker candidates was analyzed using enzyme-linked immunosorbent assays. Receiver operating characteristic curves were generated to evaluate the diagnostic accuracy of the serum biomarkers. Finally, the efficacy of prognosis efficacy of the final four biomarkers was evaluated by analyzing the clinical records. The final panel of biomarkers consisting of COPS2, CTSF, NT5E, and TERF1 provides high diagnostic power, with 95% sensitivity and 92% specificity to differentiate GC patients from healthy individuals. Prognosis analysis showed that the panel could also serve as independent predictors of the overall GC patient survival. The panel of four serum biomarkers (COPS2, CTSF, NT5E, and TERF1) could serve as a noninvasive diagnostic index for GC, and the combination of them could potentially be used as a predictor of the overall GC survival rate.
authors.affiliation: From the Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, and Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240, China; Department of Integrative Oncology, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China;
authors.forename: Lina
authors.initials: L
authors.lastname: Yang
authors.affiliation: From the Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, and Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China;
authors.forename: Jingfang
authors.initials: J
authors.lastname: Wang
authors.affiliation: From the Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, and Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China;
authors.forename: Jianfang
authors.initials: J
authors.lastname: Li
authors.affiliation: From the Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, and Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240, China;
authors.forename: Hainan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: From the Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, and Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240, China;
authors.forename: Shujuan
authors.initials: S
authors.lastname: Guo
authors.affiliation: From the Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, and Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China;
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.affiliation: From the Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, and Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China;
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China;
authors.forename: Bin
authors.initials: B
authors.lastname: Lan
authors.affiliation: Shanghai East Hospital Affiliated to Tongji University, Shanghai, 200120, China;
authors.forename: Youcheng
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Tongren Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200050, China;
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Shanghai Putuo Center Hospital, Shanghai, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Shanghai Pudong Gongli Hospital, Shanghai, China 200135;
authors.forename: Xiaonian
authors.initials: X
authors.lastname: Gu
authors.affiliation: Shanghai Fifth People's Hospital affiliated to Fudan University, Shanghai, 200240 China;
authors.forename: Chong
authors.initials: C
authors.lastname: Qi
authors.affiliation: Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205;
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Shao
authors.affiliation: From the Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, and Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China; taosc@sjtu.edu.cn byliu@sjtu.edu.cn.
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.affiliation: From the Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, and Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200240, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240, China; taosc@sjtu.edu.cn byliu@sjtu.edu.cn.
authors.forename: Sheng-Ce
authors.initials: SC
authors.lastname: Tao
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000097:blood; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000097:blood; D011379:Prognosis; D040081:Protein Array Analysis; D020543:Proteome / Q000235:genetics; D013274:Stomach Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome