| Objectives: To detect the expression of ribonucleotide reductase,an enzyme essential in DNA replication in peripheral blood of patients with chronic hepatitis B,cirrhosis,hepatocellular carcinoma,and analyze its correlation with clinical indicators.Methods: A total of 326 patients diagnosed of chronic hepatitis B,cirrhosis,hepatocellular carcinoma,and healthy volunteers were enrolled in this study,from December 2016 to June 2019,including 106 cases of chronic hepatitis B,71 cases of cirrhosis,103 cases of hepatocellular carcinoma.Among the cirrhosis group,there were33 cases with HBV infection and 38 cases not.Among the hepatocellular carcinoma group,there were 70 cases with HBV infection and 33 cases not.Also we included 46 healthy volunteers from the First Affiliated Hospital,Zhejiang University.All patients were taken serum and were measured human ribonucleotide reductase M2 peptide(RRM2)level using human ribonucleotide reductase M2 peptide(RRM2)enzyme-linked immunosorbent assay kit.All patient's general clinical situation and laboratory results related to this experiment,such as liver function,HBV-DNA,and alpha-fetoprotein were collected,RRM2 levels between the groups were compared,andthe correlation between serum RRM2 level and HBVDNA,HBsAg,ALT and other laboratory indicators were analyzed using SPSS.Results:Among the 326 eligible patients,there was no significant difference in age between the chronic hepatitis B group,the HBV related cirrhosis group and the control group.The average age of the non HBV related cirrhosis group,the HBV related liver cancer and the non HBV related liver cancer was higher than that of the control group.ELISA results showed that RRM2 levels in chronic hepatitis B(2285.02±2474.52 U/L),the HBV related liver cancer(3755.45±3294.67 U/L)and the non HBV related liver cancer(3114.87±4724.71 U/L)groups were significantly higher than those in the control group(276.09±273.79 U/L)(p<0.001).There was no significant difference in RRM2 level between the HBV related cirrhosis group(1204.24±919.93 U/L),the non HBV related cirrhosis group(207.58±233.60 U/L)and the control group.The average level of RRM2 in the chronic hepatitis B group was higher than that of the HBV related cirrhosis group,but the difference was not significant(p>0.05).The level of RRM2 in the HBV related liver cancer was significantly higher than that of chronic hepatitis B group(p<0.05)and the HBV related cirrhosis group(p<0.001).The mean RRM2 level of the HBV related cirrhosis group was higher than that of the non HBV related cirrhosis group,and the mean RRM2 level of the HBV related liver cancer was higher than that of the non HBV related liver cancer,but the difference was not significant(p>0.05).In chronic hepatitis B group,serum RRM2 level was positively correlated with HBVDNA(r=0.573,p<0.001),and serum RRM2 level was positively correlated with HBsAg level(r=0.307,p=0.022).Patients were divided according to ALT level: patients with ALT<80U/L were divided into ALT low-level group,those with ALT>80U/L were divided into ALT high-level group,then there is a positive correlation(r= 0.238,p=0.014)between RRM2 value and ALT level,suggesting a significant difference in serum RRM2 level between the ALT high-level group and the ALT low-level group.In the HBV related cirrhosis group,serum RRM2 level was positively correlated with HBVDNA(r= 0.422,p=0.014),and HBsAg level was positively correlated with serum RRM2 level(r= 0.856,p <0.001).In the HBV related liver cancer,serum RRM2 level was positively correlated with HBVDNA level(r=0.363,p=0.002),and serum RRM2 level was positively correlated with HBsAg level(r=0.266,p=0.026),and RRM2 level was positively correlated with AFP level(r=0.291,p=0.015).According to ROC curve analysis,in the HBV related liver cancer,when the value of RRM2 was 551.91 U/L,the diagnostic index was the largest,with the sensitivity of72.9%,specificity of 76.4% and area under the curve is 0.730.When the AFP value was80.95 ng/ml,the diagnostic index was the largest,the sensitivity was 48.57%,the specificity was 98.2%,and the area under the curve was 0.712.In the non HBV related liver cancer,when the value of RRM2 was 314.92 U/L,the diagnostic index was the largest,with 75% sensitivity,78.3% specificity and 0.776 area under the curve.The diagnostic index was the largest when the AFP value was 9.45 ng/ml,with the sensitivity of 68.8%,specificity of 97.8% and area under the curve of 0.859.Conclusion:(1)the level of RRM2 in chronic viral hepatitis B group,the HBV related liver cancer group and the non HBV related liver cancer group was significantly higher than that of the control group.There was no significant difference between the control group,the HBV related cirrhosis group,and the non HBV related cirrhosis group.(2)the RRM2 level of the HBV related liver cancer group was significantly higher than that of the chronic hepatitis B group,and the average RRM2 level of the chronic hepatitis B group was higher than that of the HBV related cirrhosis group,but the difference was not significant.(3)there was a positive correlation between serum RRM2 level andHBVDNA and HBsAg level in the chronic hepatitis B group,the HBV related cirrhosis group and the HBV related liver cancer group.In CHB group,there were significant differences in serum RRM2 between ALT high level group and ALT low level group.(4)Serum RRM2 level has potential value in the diagnosis of liver cancer,but it still needs to be further verified by multi-center and large-sample clinical studies. |
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