| Objective:Toinvestigatetheexpressionofdivalentmetal transporterl1(DMT1),ferroportin1(FPN1),superoxide dismutase2(SOD2)and glutathione peroxidase1(GPx1)in hepatocellular carcinoma(HCC),and to analyze the relationship between the four proteins and the clinicopathological features,especially the recurrence and metastasis of hepatocellular carcinoma,and to explore the predictive role of these four proteins in the recurrence,metastasis and progression of HCC.Methods:For this study,the paraffin specimens of 94 patients with HCC underwent radical resection and pathological diagnosis of HCC were collected.Immunohistochemistry(IHC)was used to detect the expression of DMT1,FPN1,GPx1 and SOD2 proteins in hepatocellular carcinoma tissues and corresponding adjacent tissues;the expression of each protein in different tissues was observed by optical microscope,and scored them at high-power microscope.Collected the clinical and pathological data of 94 patients with hepatocellular carcinoma,and follow-up was conducted to obtain their survival time.SPSS17.0 software was used for all statistical analysis.T test was used to analyze the difference of protein expression levels between the HCC and its paired paracancer.The chi-square test and spearman correlation were performed to determine the correlation of each protein expression with the patients’clinicopathological features.The Kaplan-Meier method and log-rank test were used to analyze survival of HCC patients.To determine if each protein is an independent factor of survival and recurrence,univariate and multivariate survival analyses were performed using the Cox proportional hazards regression model.The P value less than 0.05 was defined as statistically significant for all statistical analyses.Results:(1)DMT1 was mainly distributed in the cytoplasm and nucleus.In HCC tissues DMT1 average score was 5.13?3.32,high expression rate was77.7%,and in the corresponding paracarcinomatous tissues DMT1 average score was 1.94?2.91,high expression rate was only 11.7%,the difference were statistically significant(t=7.32,P=0.000;χ~2=82.723,P=0.000).The High expression group of DMT1 was associated with Edmondson-SteinerⅢ-Ⅳ(χ~2=6.274,P=0.012)and tumor capsule invasion(χ~2=5.764,P=0.016).The high DMT1 expression group,the median OS and RFS were 23.06 months and 10.32months,and the low DMT1 expression group,the median OS and RFS were30.23 months and 24.67 months,the difference were statistically significance(P=0.013,P=0.025).Cox regression model risk factor analysis showed that DMT1 was an independent factor affecting the OS and RFS of HCC patients(P=0.048,P=0.047).The high DMT1 expression group,for 1 year,2 years and 3years,the cumulative recurrence rate and cumulative mortality rate were 50.8%,50.8%,100%,13.9%,30.6%and 48.4%,and the low DMT1 expression group,for 1 year,2 years and 3 years,the cumulative recurrence rate and cumulative mortality rate were 28.6%,28.6%,46.7%,0%,5%and 14.5%,respectively.The differences between the high DMT1 expression group and low expression group,the cumulative recurrence rate and cumulative mortality rate at each time point were statistically significant(P=0.002,P=0.013).There was a significant high expression of DMT1 in the cancer tissue of recurrent or metastases group compared with non-recurrence group(χ~2=5.180,P=0.023).(2)FPN1 was mainly distributed in the cytoplasm and cell membrane.In HCC tissues FPN1 average score was 4.22?3.29,low expression rate was73.4%,and in the corresponding paracarcinomatous tissues FPN1 average score was 5.90?3.50,low expression rate was only 21.3%,the difference was statistically significant(t=4.56,P=0.001;χ~2=51.230,P=0.000).The low expression of FPN1 was associated with Edmondson-SteinerⅢ-Ⅳ(χ~2=5.390,P=0.020),TNM stageⅢ(χ~2=4.652,P=0.031)and serum HBsAg negative(χ~2=4.514,P=0.033).The low FPN1 expression group,the median OS and RFS were 24.64 months and 8.48 months,respectively,the high FPN1 expression group,the median OS and RFS were 25.10 months and 24.44 months,the difference was statistical significance(P=0.030,P=0.005).Cox regression model risk factor analysis showed that FPN1 was an independent factor affecting the RFS of hepatocellular carcinoma(P=0.029),but not an independent factor affecting OS(P=0.075).The low FPN1 expression group,for 1 year,2 years and 3 years,the cumulative of recurrence rate and cumulative mortality rate were 60.7%,67.3%,84%,13.5%,29.9%and 45.4%,and the high FPN1 expression group,for 1 year,2 years and 3 years,the cumulative of recurrence rate and cumulative mortality rate were 4%,22.1%,61.1%,0%,9.1%and 9.1%,the differences between high FPN1 expression group and low expression group,the cumulative recurrence rate and cumulative mortality rate at each time point were statistically significant(P=0.000,P=0.03).FPN1expression was significantly lower in patients with recurrence or metastatic(χ~2=17.897,P=0.000).(3)SOD2 was mainly distributed in the cytoplasm.In HCC tissues SOD2average score was 3.44?2.02,low expression rate was 78.7%,and in the corresponding paracarcinomatous tissues SOD2 average score was 5.65?2.99,low expression rate was only 36.2%,the difference was statistically significant(t=6.84,P=0.001;χ~2=34.815,P=0.000).The low expression of SOD2 was significantly correlated with tumor diameter>5cm(χ~2=6.249,P=0.012)and macrovascular invasion(χ~2=12.634,P=0.000).In the high SOD2 expression group,the median OS and RFS were 29.16 months and 23.61 months,respectively,and the low SOD2 expression group,the median OS and RFS were23.56 months and 10.38 months,respectively,the differences were statistically significant(P=0.042,P=0.017).Cox risk regression model analysis showed that SOD2 was not an independent factor in the prognosis of hepatocellular carcinoma(P=0.230,P=0.188).The high SOD2 expression group and low expression group,for 1 year,2 years and 3 years,the cumulative recurrence rate were 35.0%,45.0%,75.6%,48.7%,58.3%and 72.6%,respectively,there was no significant difference between the two groups(P=0.218),but the cumulative mortality rate,for 1 year,2 years and 3 years,were 0%,10.0%,10.0%,12.7%,29.0%and 52.7%,respectively,the difference was statistically significant(P=0.017).There was no significant difference in the expression of SOD2 between recurrence and non-recurrence(χ~2=0.002,P=0.965).(4)GPx1 was mainly distributed in the cytoplasm and nucleus.In HCC tissue GPx1 average score was 3.38?2.88,low expression rate was 72.3%,and in the corresponding paracarcinomatous tissues GPx1 average score was3.79?2.97,low expression rate was only 44.7%,the difference was statistically significant(t=8.118,P=0.000;χ~2=14.812,P=0.000).The low expression of GPx1 was related to TNM stageⅢ(χ~2=5.184,P=0.023).In the patients of low GPx1 expression,the median OS and RFS were 23.29 months and 9.97months,respectively,and the patients of high GPx1 expression,the median OS and RFS were 27.56 months and 24.77 months,respectively,he differences were statistically significant(P=0.006,P=0.008).Cox risk regression analysis showed that GPx1 was an independent factor in the prognosis of hepatocellular carcinoma(P=0.030,P=0.035).Patients with low GPx1 expression,for 1 year,2 years and 3 years,the cumulative recurrence rate and cumulative mortality rate were 55.7%,62.7%,87.4%,13.7%,32.9%and 47.5%,respectively,patients with high GPx1 expression for 1 year,2 years and 3 years,the cumulative recurrence rate and the cumulative mortality rate were 19.9%,36.1%,48.9%,0%,4.0%and 17.7%,respectively,the differences at each time point were statistically significant(P=0.006,P=0.006).Recurrence or metastatic patients were significantly lower in GPx1(χ~2=6.652,P=0.01).Conclusions:(1)In HCC tissue,DMT1 was mainly high expression,and FPN1is mainly low expression,and they were related with differentiation,invasion and other malignant biological behavior;(2)The expression of FPN1 in HCC tissues was not the independent factors of OS in HCC patients after radical resection,and the expression of DMT1 was an independent prognosis factor of HCC patients,and the prognosis of patients with high expression was poor.(3)In HCC tissue,SOD2 and GPx1 were mainly low expression,and they were related with the development of HCC,vascular invasion and other malignant biological behavior;(4)The expression of SOD2 was not an independent prognostic factors in patients with HCC after radical resection,and the expression of GPx1 was an independent prognosis factor of HCC patients,and the prognosis of patients with low expression was poor. |
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