Zhou Ni, Wang Kuifeng, Fang Shanhua, Zhao Xiaoyu, Huang Tingting, Chen Huazhong, Yan Fei, Tang Yongzhi, Zhou Hu, Zhu Jiansheng
Department of Infectious Diseases, Affiliated Taizhou Hospital of Wenzhou Medical University, Taizhou, China.
E-Institute of Shanghai Municipal Education Committee, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Physiol. 2017 Dec 6;8:1009. doi: 10.3389/fphys.2017.01009. eCollection 2017.
Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF), characterized by an acute deterioration of liver function in the patients with chronic hepatitis B (CHB), is lack of predicting biomarkers for prognosis. Plasma is an ideal sample for biomarker discovery due to inexpensive and minimally invasive sampling and good reproducibility. In this study, immuno-depletion of high-abundance plasma proteins followed by iTRAQ-based quantitative proteomic approach was employed to analyze plasma samples from 20 healthy control people, 20 CHB patients and 20 HBV-ACLF patients, respectively. As a result, a total of 427 proteins were identified from these samples, and 42 proteins were differentially expressed in HBV-ACLF patients as compared to both CHB patients and healthy controls. According to bioinformatics analysis results, 6 proteins related to immune response (MMR), inflammatory response (OPN, HPX), blood coagulation (ATIII) and lipid metabolism (APO-CII, GP73) were selected as biomarker candidates. Further ELISA analysis confirmed the significant up-regulation of GP73, MMR, OPN and down-regulation of ATIII, HPX, APO-CII in HBV-ACLF plasma samples ( < 0.01). Moreover, receiver operating characteristic (ROC) curve analysis revealed high diagnostic value of these candidates in assessing HBV-ACLF. In conclusion, present quantitative proteomic study identified 6 novel HBV-ACLF biomarker candidates and might provide fundamental information for development of HBV-ACLF biomarker.
乙型肝炎病毒（HBV）相关慢加急性肝衰竭（HBV-ACLF）的特征是慢性乙型肝炎（CHB）患者肝功能急性恶化，目前缺乏用于预后预测的生物标志物。血浆是发现生物标志物的理想样本，因为其采样成本低、侵入性小且具有良好的可重复性。在本研究中，采用高丰度血浆蛋白免疫去除法结合基于iTRAQ的定量蛋白质组学方法，分别对20名健康对照者、20名CHB患者和20名HBV-ACLF患者的血浆样本进行分析。结果，从这些样本中共鉴定出427种蛋白质，与CHB患者和健康对照者相比，有42种蛋白质在HBV-ACLF患者中差异表达。根据生物信息学分析结果，选择了6种与免疫反应（MMR）、炎症反应（OPN、HPX）、血液凝固（ATIII）和脂质代谢（APO-CII、GP73）相关的蛋白质作为生物标志物候选物。进一步的ELISA分析证实，在HBV-ACLF血浆样本中，GP73、MMR、OPN显著上调，而ATIII、HPX、APO-CII显著下调（<0.01）。此外，受试者工作特征（ROC）曲线分析显示，这些候选物在评估HBV-ACLF方面具有较高的诊断价值。总之，目前的定量蛋白质组学研究鉴定出6种新型HBV-ACLF生物标志物候选物，可能为HBV-ACLF生物标志物的开发提供基础信息。
