Oncotarget. 2017 May 2. doi: 10.18632/oncotarget.17546. [Epub ahead of print]
Circulating soluble programmed death-1 levels may differentiate immune-tolerant phase from other phases and hepatocellular carcinoma from other clinical diseases in chronic hepatitis B virus infection.
Li N1, Zhou Z1, Li F1, Sang J1, Han Q1, Lv Y2,3, Zhao W1, Li C1, Liu Z1,3.
Author information
1 Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an 710061, Shaanxi, China.
2 Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
3 Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi' an 710061, Shaanxi, China.
Abstract
Programmed death-1 (PD-1) is involved in the immune dysfunction of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study analyzed the association of circulating soluble PD-1 (sPD-1) levels with the phases and clinical diseases in chronic HBV infection. Serum sPD-1 levels were determined by enzyme linked immunosorbent assay in patients with different phases and liver diseases of chronic HBV infection. The sPD-1 levels in patients with chronic HBV infection were significantly elevated compared with HBV infection resolvers or healthy controls. According to phases, sPD-1 level in immune-tolerant phase (IT) was significantly lower than in other phases. Multivariate analysis showed that sPD-1 was an independent factor associated with IT. Area under the receiver operating characteristic (ROC) curves (AUC) showed that sPD-1 was significantly discriminative of IT from other phases with a cut-off of 1.535 ng/mL (AUC, 0.984; P<0.001). According to clinical diseases, sPD-1 level in HBV-related HCC was significantly higher than in other clinical diseases. Multivariate analysis showed that sPD-1 was an independent factor associated with HCC. The sPD-1 was significantly discriminative of HCC from other clinical diseases with a cut-off of 6.058 ng/mL (AUC, 0.962; P<0.001). The sPD-1 levels were significantly associated with HCC patients' overall survival. HCC resection resulted in remarkable reduction in sPD-1 levels. These results demonstrate the involvement of sPD-1 in the disease course of chronic HBV infection and indicate the potential to apply sPD-1 as a biomarker for differentiating IT from other phases and HCC from other disease conditions in chronic HBV infection.
KEYWORDS:
程序性死亡-1(PD-1)涉及乙型肝炎病毒(HBV)感染和肝细胞癌(HCC)的免疫功能障碍。本研究分析了循环可溶性PD-1(sPD-1)水平与慢性HBV感染期和临床疾病的关系。血清sPD-1水平通过酶联免疫吸附测定法测定慢性HBV感染患者不同期和肝病。慢性HBV感染患者的sPD-1水平与HBV感染症候群或健康对照相比显着升高。根据阶段,免疫耐受期(IT)中的sPD-1水平显着低于其他阶段。多变量分析表明,sPD-1是与IT相关的独立因素。受试者工作特征(ROC)曲线(AUC)下的面积显示,sPD-1与其他相显着区别于IT,其间隔为1.535ng / mL(AUC,0.984; P <0.001)。根据临床疾病,HBV相关HCC的sPD-1水平明显高于其他临床疾病。多变量分析显示sPD-1是与HCC相关的独立因素。 sPD-1与其他临床疾病的HCC有显着差异,截止值为6.058 ng / mL(AUC,0.962; P <0.001)。 sPD-1水平与HCC患者的总体生存率显着相关。 HCC切除导致sPD-1水平显着降低。这些结果表明sPD-1参与慢性HBV感染的疾病过程,并表明将sPD-1应用于将IT与其他阶段和HCC与慢性HBV感染中其他疾病状况区分开来的生物标志物的潜力。
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