Clinical Significance And Expression Of Blood CYLD,GOLPH3 And NF-κB Signal-related MRNA In Primary Hepatocellular Carcinoma

Objective: We analyzed the expression level of CYLD,GOLPH3,NF-κB1 and Rel A mRNA in peripheral blood of healthy individuals,hepatitis,liver cirrhosis and hepatocellular carcinoma(HCC)patients and the relationship between CYLD,GOLPH3 mRNA expression level and clinical characteristics in HCC patients.Then,we further analyze the clinical values of AFP,CYLD,GOLPH3,NF-κB1 and Rel A in diagnosing HCC by receiver operating characteristic(ROC)curves.Methods: In this study,a total of 257 blood samples including 90 patients with HCC,41 patients with liver cirrhosis,46 chronic hepatitis patients,and 80 healthy individuals were enrolled from January 2016 to October 2016.The expression levels of CYLD,GOLPH3,NF-κB1 and Rel A mRNA in peripheral blood of subjects were detected by fluorescence quantitative PCR.The serum level of STB,AST and ALT was detected by automatic biochemical analyzer.Immunochemical luminescence was used to serum AFP level.All the data were statistically analyzed using the SPSS software version 17.0.To determine the optimal cut-off value for diagnosis of HCC,receiver operating characteristic(ROC)curves were constructed,and comparisons were tested using the U test.At the same time,GEP model was used to analyze the diagnostic value of four indicators for HCC.Results: The median expression level of CYLD mRNA was 0.023 in the HCC group,significantly lower than that in the liver cirrhosis group,hepatitis group,and healthy control group,while the relative expression of CYLD mRNA in patients with cirrhosis was significantly higher than that in normal and hepatitis patients.Meanwhile,GOLPH3,NF-κB1 and RELA in the HCC group significantly higher than that in the liver cirrhosis group,hepatitis group,and healthy control group.In HCC group,the blood levels of CYLD mRNA were strongly reduced in patients with bigger tumor and high transaminase levels.Meanwhile,patients with tumor metastases,III / IV stage and high Ki67 indices displayed significantly higher blood GOLPH3 mRNA level.NF-ΚB1 and Rel A mRNA were highly expressed in the blood of patients with stage III/IV,and patients with high Ki67 indices and portal vein tumor thrombus displayed significantly higher blood Rel A mRNA level.The AUROC curve for AFP,CYLD,GOLPH3,NF-ΚB1was 0.828,0.847,0.677,0.658 and 0.623,respectively.the AUROC curve for the combination of AFP+CYLD was 0.897.The diagnostic value of joint indicator is better than single diagnosis of AFP or CYLD(P<0.001).Further analysis showed that CYLD has diagnostic value for HCC patients with AFP-negative.Conclusion: 1.The relative expression of CYLD mRNA in HCC group was significantly reduced.Meanwhile,the relative expression of CYLD mRNA was significantly higher in patients with liver cirrhosis than that in normal and hepatitis patients.The blood GOLPH3,NF-κB1 and Rel A mRNA level was significantly higher than that in the other three groups.2.The relative expression of CYLD mRNA was decreased in the patients with higher tumor size and higher serum transaminase level.The relative expression of GOLPH3 mRNA was increased in the patients with metastatic,III / IV stage and high Ki67 index.The relative expression of NF-κB1 mRNA was increased in patients with stage III / IV.The relative expression of Rel A mRNA was elevated in patients with portal vein tumor thrombus,III / IV and high Ki67 index.3.CYLD has accuracy in the early diagnosis of liver cancer.The combined diagnostic value of AFP and CYLD is significantly higher than that of AFP or CYLD alone.CYLD has diagnostic value for HCC patients with AFP-negative.