摘要
目的基于高密度抗体芯片技术检测肝癌(肝细胞癌,HCC)血清的蛋白表达图谱和潜在生物标志物。方法运用由1000个血清蛋白抗体组成的抗体芯片结合生物素标记血清的策略,对健康人和乙型肝炎、肝硬化、HCC[甲胎蛋白(α-fetoprotein,AFP)阴性]4组样本的血清蛋白表达图谱进行检测,通过one-way ANOVA统计方法分析差异蛋白,用实验室点制的小型芯片对检测的差异蛋白进行验证。结果该抗体芯片技术可用于HCC血清蛋白表达图谱的检测,且有很好的重复性和特异性。通过小型芯片的验证发现了AFP、癌胚抗原125(CA125)、Myc诱导核抗原(MINA)和D-二聚体(D-dimer) 4个潜在生物标志物,其中MINA和D-dimer分别与肝硬化和HCC密切相关(P≤0. 01)。另外,生存曲线分析发现MINA和D-dimer对HCC可能具有一定的预后价值(P≤0. 05)。结论通过抗体芯片的方法可初步筛选出具有临床诊断意义的HCC血清标志物,为进一步开展临床验证奠定基础。
Objective To detect the protein expression profile and identify potential biomarkers of liver cancer( hepatocellular carcinoma,HCC) serum based on antibody microarray. Methods The antibody microarray composed of1000 serum protein antibodies was used to detect the samples of healthy humans,hepatitis,cirrhosis,and HCC(α-fetoprotein,AFP-) together with biotin-labeling of the serum proteins. The differentially expressed proteins were identified by one-way ANOVA with a P value of 0. 01 and verified by custom array fabricated in laboratories. Results The antibody microarray could detect the serum protein expression profiles with good repeatability and specificity. Four potential biomarkers AFP,carcinoembryonic antigen125( CA125),Myc-induced nuclear antigen( MINA),and D-dimer were confirmed using custom antibody arrays,in which MINA and D-dimer were closely related to cirrhosis and HCC,respectively( P≤0. 01). Therefore,MINA and D-dimer were of potential value in the prognosis in liver cancer( P ≤0. 05). Conclusion This antibody microarray method can be used to screen liver cancer serum markers of great clinical significance.
作者
许萌
王红叶
代佳宇
赵晓航
牟劲松
刘伟
孙薇
许丹科
于晓波
XU Meng;WANG Hong-ye;DAI Jia-yu;ZHAO Xiao-hang;MOU Jin-song;LIU Wei;SUN Wei;XU Dan-ke;YU Xiao-bo(State Key Laboratory of Analytical Chemistry for Life Sciences,School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210023,China;State Key Laboratory of Proteomics,Beijing Proteome Research Center,National Center for Protein Sciences,Institute of Lifeomics,Academy of Military Medical Sciences,Academy of Military Sciences, Beijing 102206,China;State Key Laboratory of Molecular Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;ICU of the Fifth Medical Center of PLA General Hospital,Beijing 100039,China;Hepatopancreatobiliary Surgery,Key Laboratory of Carcinogenesis and Translational Research,Ministry of Education,Peking University School of Oncology,Beijing Cancer Hospital and Institute,Beijing 100142,China)
出处
《军事医学》
CAS
CSCD
北大核心
2018年第12期903-909,共7页
Military Medical Sciences
基金
国家重大专项资助项目(2018ZX09733003,2017YFC0906703,2018YFA0507503)
国家自然科学基金资助项目(31870823,81673040)
蛋白质组学国家重点实验室资助项目(SKLP-K201505,SKLP-0201504,SKLP-0201703).
关键词
肝癌
抗体芯片
生物学标记
蛋白表达图谱
甲胎蛋白类
癌胚抗原
hepatocellular carcinoma
antibody microarray
biological markers
protein expression profile
alphafetoproteins
carcinoembryonic antigen
