Expression And Clinical Value Of Serum Trypsin Inhibitor Kazal1 In Patients With Hepatocellular Carcinoma

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).The expression levels of SPINK1 in the serum of the above three groups and in the supernatant of HepG2.2.15,HepG2,Huh7 and LO2 cells were measured by ELISA.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.Disease-free survival(DFS)and overall survival(OS)were counted as short-term prognostic indicators.Risk factors for the DFS and OS of patients with HCC were assessed by Kaplan-Meier and Cox regression analysis.Results Serum levels of SPINK1 and AFP were increased in the HCC group compared to the chronic liver disease and health control groups(?~2=87.279?72.545,all of them P<0.01).Serum SPINK1 levels in chronic liver disease group were similar to that in healthy control group(P>0.05).SPINK1 levels in HepG2.2.15 cells was significantly higher as compared to that in other cells(2.85±0.03 versus 1.54±0.04,1.50±0.04,0.9±0.04 ng/m L;P<0.001).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 were 71.18%and 95%(when the cut-off value was 1.75ng/m L).Serum SPINK1 levels were different among HCC patients with different Child-Pugh grades(?~2=10.17,P<0.05).Short-time DFS and OS of HCC patients 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(hazard ratio=9.92,95%CI:2.82?34.87;P<0.01)in HCC patients.Serum SPINK1 level was also an independent risk factor for short-time OS(hazard ratio=3.23,95%confidence interval,1.49?7.02;P<0.01).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.