The Expression And Clinical Significance Of Nei-Like DNA Glycosylase 3 In Hepatocellular Carcinoma

Objective: The aim of this study was to investigate the expression profile of Nei like DNA glycosylase 3(NEIL3)and its clinical relevance in HCC.Methods: Bioinformatics methods were used to analyze the expression level of NEIL3 in HCC and its adjacent tissues.A total of 130 HCC and corresponding nontumor tissues were collected to perform immunohistochemistry(IHC).mRNA levels in 12 pairs of hepatocellular carcinoma and non-tumor tissue specimens were measured using quantitative real time polymerase chain reaction(qRT-PCR).The expression level of NEIL3 in seven human hepatocarcinoma cell lines and normal hepatocyte lines was detected by qRT-PCR and western blotting.The clinical relevance and prognostic value of NEIL3 in HCC was analyzed by the Chi-Square test,Kaplan-Meier analysis,the Cox proportional hazard model and nomogram.Results:1.Bioinformatics analysis showed that NEIL3 expression level increased significantly in HCC patients compared with non-tumor tissues(P<0.001).2.IHC showed that the NEIL3 protein level was remarkably upregulated in tumor tissues compared with nontumor tissues(fold change =1.24,P<0.001).3.Quantitative real time polymerase chain reaction results showed that the expression of NEIL3 mRNA in tumor tissues was significantly higher than that in non-tumor tissues.4.Western blot results showed that the expression level of NEIL3 protein in HCC tissues was higher than that of corresponding paracancerous tissues.5.The results of statistical analysis showed that high NEIL3 expression was significantly correlated with BCLC stage(P=0.00)and TNM stage(P=0.005).6.The survival analysis showed that the overall survival rate(OS)and disease free survival rate(DFS)rates in the high NEIL3 expression group were significantly worse than those in the low NEIL3 expression group(P=0.007 and P=0.004).7.Subgroup analysis showed that high NEIL3 expression predicted worse OS and DFS for HCC patients with advanced TNM stage,poorly differentiated tumor,HBsAg positive or cirrhosis.8.Multivariate analysis and the prognostic nomograms revealed that tumor NEIL3 level may serve as a promising prognostic indicator for OS and DFS in HCC patients.Conclusions:1.NEIL3 is highly expressed in hepatocellular carcinoma tissue compared with normal liver tissue.2.The overall survival rate and disease free survival rate of hepatocellular carcinoma patients with high NEIL3 expression were worse than those with low NEIL3 expression.3.NEIL3 can be used as a prognostic factor in patients with hepatocellular carcinoma.