SPINK1在肝细胞癌中的表达及临床价值研究

Expression and clinical value of serum trypsin inhibitor Kazal1 in patients with hepatocellular carcinoma

目的检测丝氨酸蛋白酶抑制剂Kazal1(SPINK1)在肝细胞癌(HCC)中的表达水平,分析SPINK1单独及联合甲胎蛋白(AFP)检测对HCC的诊断效能,探讨SPINK1在HCC短期预后评估中的价值。方法收集HCC组患者(87例)、慢性肝病组患者(73例)及健康对照组志愿者(45例)血清。采用Kruskal-Wallis H检验比较SPINK1在各组的表达水平,并分析其与HCC患者Child-Pugh分级的关系;绘制ROC曲线分析SPINK1、AFP及两者联合检测对HCC的诊断效能;采用Kaplan-Meier法和Cox回归模型分析HCC无病生存期(DFS)的危险因素。结果HCC组血清SPINK1及AFP水平高于慢性肝病组及健康对照组(χ^2=87.28、72.55,P<0.01),且SPINK1在慢性肝病组和健康对照组间差异无统计学意义(P>0.05)。SPINK1诊断HCC的敏感度高于AFP,两者ROC曲线下面积(AUC)差异无统计学意义(P>0.05)。联合检测的特异度及AUC均高于单项检测(P<0.05)。SPINK1辅助诊断AFP阴性HCC的AUC为81.70%(95%CI:0.74~0.88),取cut-off值为1.75 ng/ml时,特异度为71.18%,敏感性为95%。不同Child-Pugh分级HCC患者血清SPINK1水平差异有统计学意义(χ2=10.17,P<0.05)。血清SPINK1高水平组HCC患者短期DFS低于低水平组(P<0.01),血清SPINK1(HR=9.92,95%CI,2.82~34.87,P<0.01)是HCC患者短期DFS的独立危险因素。结论血清SPINK1对HCC有较高的诊断价值,并且在AFP阴性HCC的诊断中具有重要补充诊断意义。高水平SPINK1对HCC的短期不良预后具有较高预测价值。

Objective To investigate the expression of serum SPINK1 in hepatocellular carcinoma(HCC)patients,analyze the diagnostic efficacy of SPINK1 alone and combined with alpha fetoprotein(AFP)detection in HCC,and explore the value of SPINK1 in the short-term prognosis of HCC.Methods Serum was collected from patients in the HCC group(87 cases),patients in the chronic liver disease group(73 cases),and volunteers in the healthy control group(45 cases).Kruskal-Wallis H was used to compare the expression of SPINK1 among different groups,and analyze its relationship with Child-Pugh grades in HCC patients;the ROC curve was drawn and used to analyze the diagnostic efficacy of SPINK1,AFP and the combined detection for HCC.Risk factors for the Disease-free survival(DFS)of HCC were assessed by Kaplan-Meier and Cox regression analysis.Results Serum levels of SPINK1 and AFP were higher in the HCC group than those in the chronic liver disease and health control groups(χ^2=87.28,72.55,all P<0.01).Serum SPINK1 levels in chronic liver disease group were similar to those in healthy control group(P>0.05).The sensitivity of SPINK1 in the diagnosis of HCC was higher than that of AFP.There was no difference in AUC between the two biomarkers(P>0.05).The specificity and AUC of the combined were higher than that of any single one(P<0.05).The AUC of SPINK1 in the diagnosis of AFP-negative HCC was 81.70%(95%CI:0.74-0.88),with the specificity and sensitivity as 71.18%and 95%(when the cut-off value was 1.75 ng/ml).Serum SPINK1 levels were different among HCC patients with different Child-Pugh grades(χ^2=10.17,P<0.05).Short-time DFS of HCC in the high SPINK1 group was lower than that of the low SPINK1 group(P<0.01),Serum SPINK1 level was an independent risk factor for short-time DFS(HR=9.92,95%CI:2.82-34.87,P<0.01)in HCC patients.Conclusion Serum SPINK1 has high diagnostic value for HCC,especially in the diagnosis of AFP-negative HCC.Higher levels of SPINK1 have a high predictive value for short-time poor prognosis of HCC.