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使用人类蛋白质组芯片鉴定用于胃癌诊断的血清生物标志物

Identification of Serum Biomarkers for Gastric Cancer Diagnosis Using a Human Proteome Microarray.

作者信息

Yang Lina, Wang Jingfang, Li Jianfang, Zhang Hainan, Guo Shujuan, Yan Min, Zhu Zhenggang, Lan Bin, Ding Youcheng, Xu Ming, Li Wei, Gu Xiaonian, Qi Chong, Zhu Heng, Shao Zhifeng, Liu Bingya, Tao Sheng-Ce

机构信息

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;

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;

出版信息

Mol Cell Proteomics. 2016 Feb;15(2):614-23. doi: 10.1074/mcp.M115.051250. Epub 2015 Nov 23.

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.

摘要

我们旨在全球范围内发现用于诊断胃癌(GC)的血清生物标志物。利用来自独立患者队列的血清样本发现并验证了GC血清自身抗体,该队列包括1401名参与者,分为三组,即健康组、GC患者组和GC相关疾病组。为了发现GC的生物标志物,首先应用人类蛋白质组微阵列对来自GC患者和健康对照的总共87份血清样本中的特异性自身抗体进行筛选。通过统计分析方案确定潜在的生物标志物。构建仅含有潜在生物标志物的靶向蛋白质微阵列,并使用914份样本对候选生物标志物进行验证。为了提供进一步的验证,使用酶联免疫吸附测定法分析候选生物标志物特异性自身抗体的丰度。生成受试者工作特征曲线以评估血清生物标志物的诊断准确性。最后,通过分析临床记录评估最终四种生物标志物的预后疗效。由COPS2、CTSF、NT5E和TERF1组成的最终生物标志物组具有很高的诊断能力,区分GC患者和健康个体的灵敏度为95%,特异性为92%。预后分析表明,该生物标志物组还可作为GC患者总体生存的独立预测指标。四种血清生物标志物(COPS2、CTSF、NT5E和TERF1)组成的生物标志物组可作为GC的非侵入性诊断指标,它们的组合可能用作GC总体生存率的预测指标。

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