肝细胞癌患者血清HSP90α和PIVKA-Ⅱ水平变化及其临床意义探讨

Application of serum HSP90α and PIVKA-II levels in prognosis of patients with hepatocellular carcinoma

目的探讨热休克蛋白90α(HSP90α)和维生素K拮抗剂诱导蛋白-Ⅱ(PIVKA-Ⅱ)在肝细胞癌(HCC)患者血清变化及在预后评估中的价值。方法2014年1月~2016年6月我院诊治的HCC患者112例、乙型肝炎肝硬化患者96例、慢性乙型肝炎患者82例和健康体检者84例,所有肝癌患者接受经肝动脉化疗栓塞术,采用ELISA法检测血清HSP90α和PIVKA-Ⅱ水平,采用多元Logistic回归分析影响3 a生存的因素,应用ROC曲线评估血清HSP90α和PIVKA-Ⅱ单独或联合预测HCC患者3 a生存率的价值。结果HCC组血清HSP90α和PIVKA-Ⅱ水平分别为(61.6±5.0)ng/mL和(832.6±66.7)mAU/mL,显著高于乙型肝炎肝硬化组[分别为(13.2±1.6)ng/mL和(29.4±2.9)mAU/mL,P<0.05]、慢性乙型肝炎组[分别为(4.3±0.4)ng/mL和(29.1±3.0)mAU/mL,P<0.05]或健康人组[分别为(3.2±0.4)ng/mL和(26.7±3.2)mAU/mL,P<0.05];入组时55例生存组血清HSP90α和PIVKA-Ⅱ水平分别为(44.4±4.4)ng/mL和(701.3±62.3)mAU/mL,显著低于57例死亡组[分别为(78.3±5.2)ng/mL和(959.2±92.2)mAU/mL,P<0.05];单因素分析表明肝外转移、肿瘤分化程度、Child-Pugh分级、TNM分期、血清HSP90α和PIVKA-Ⅱ水平影响HCC患者生存,而多因素Logistic回归分析发现,肝外转移、肿瘤分化程度低、Child-Pugh C级、TNMⅢ~Ⅳ期、血清HSP90α和PIVKA-Ⅱ水平高为影响HCC患者3 a生存率的独立危险因素(P<0.05);ROC曲线分析结果显示血清HSP90α和PIVKA-Ⅱ单独预测HCC患者3 a生存率的AUC分别为0.814和0.836,显著低于两者联合预测的0.929(P<0.05)。结论血清HSP90α和PIVKA-Ⅱ水平影响肝细胞癌患者生存,对于高水平者,应密切观察其病情变化,并及时给予适当的干预。

Objective The aim of this study was to explore the value of serum heat shock protein 90α( HSP90α) and protein-induced by vitamin K antagonist-II( PIVKA-Ⅱ) in prognosis of patients with hepatocellular carcinoma( HCC). Methods A total of 112 patients with HCC,96 patients with hepatitis B liver cirrhosis,82 patients with chronic hepatitis B,and 84 healthy persons were enrolled in our hospital between January 2014 and June 2016,and all patients with HCC underwent transcatheter arterial chemoembolization( TACE). Serum HSP90α and PIVKA-Ⅱ levels were detected by ELISA. The ROC was applied to evaluate the efficacy of serum parameters for the prognosis of patients with HCC after TACE. Results Serum Hsp90 α and PIVKA-Ⅱ levels in HCC group were( 61.6±5.0) ng/m L and( 832.6±66.7) m AU/m L,significantly higher than [13.2±1.6]ng/m L and( 29.4±2.9) m AU/m L,P < 0.05]in patients with cirrhosis,or [4.3±0.4) ng/m L and( 29.1±3.0) m AU/m L,P<0.05]in patients with hepatitis B or [( 3.2±0.4) ng/m L and( 26.7±3.2) m AU/m L,P<0.05] in healthy persons;serum Hsp90 α and PIVKA-Ⅱ levels in 55 survivals were( 44.4±4.4) ng/m L and( 701.3±62.3) m AU/m L,respectively,which were significantly lower than [( 78.3± 5. 2) ng/m L and( 959. 2 ± 92. 2) m AU/m L,P < 0. 05] in 57 dead;univariate analysis showed that extrahepatic metastasis,tumor cell differentiation,Child-Pugh classification,TNM staging,and serum HSP90α and PIVKA-Ⅱ levels were significantly different in survivals and dead,and the multivariate Logistic regression analysis showed that extrahepatic metastasis,low tumor differentiation,Child-Pugh class C,TNM Ⅲ-Ⅳ staging,as well as serum high HSP90α and PIVKA-Ⅱ levels were the independent risk factors for poor three-year survival rate( P < 0. 05);the results of ROC curve analysis showed that the AUC of serum HSP90α and PIVKA-Ⅱ combination for predicting three-year survival were 0.929,significantly higher by anyone alone( the AUC were 0.814 and 0.836,respectively,P<0.05). Conclusion Serum HSP90α and PIVKA-Ⅱ levels are closely related to the outcomes of patients with HCC after TACE therapy,and the increased serum levels of the two parameters hints poor prognosis of patients with HCC,which should deal with appropriately in clinical practice.