Study On The Relationship Between Expression Of Neuregulin Receptor Degradation Protein-1(Nrdp1)and Biological Behavior Of Tumor In Hepatocellular Carcinoma

Objective This study is aimed to investigate the potential role of the neuregulin receptor degradation protein-1(Nrdp1)in the pathology of hepatocellular carcinoma(HCC).Methods Western blot was performed to determine the expression of Nrdp1 in HCC tissues and proliferating HCC cells.The detailed involvement of Nrdp1 in the regulation of HCC proliferation was further explored using Nrdp1-targeting small interfering RNA(siRNA).Specimens of 89 HCC patients undergoing hepatic resection were evaluated for Nrdp1 expression using immunohistochemistrical assay and the correlation between Nrdp1 expression and clinicopathological factors of the patients was determined by statistical analysis to determine the prognostic merit of nrdp1 expression in HCC.Results Nrdp1 protein was significantly down-regulated in HCC tissues compared with adjacent normal liver ones.Immunohistochemical analysis showed that the expression of Nrdp1 was negatively correlated with Ki-67 levels in HCC specimens(r=0.857;P<0.05).Furthermore,statistical analysis indicated down-regulated Nrdp1 expression was significantly assoicated with greater maximal tumor size(P<0.05)and higher histological grade(P<0.05).Using Kaplan-Meier analysis,we proved that high Nrdp1 expression predicted significantly better patients' survival than low Nrdp1 expression(P<0.05).In addition,we found that Nrdp1 was accumulated in serum-starved Hep G2 hepatocytes,and was progressively decreased after serum-refeeding.Moreover,interference of Nrdp1 expression using si RNA oligos led to impaired proliferation of HepG2 cell.Conclusions Nrdp1 was markedly down-regulated in HCC tissues.The expression of Nrdp1 was correlated with tumor size and histological grade.Low expression of Nrdp1 predicted poor prognosis of HCC patients,suggesting that Nrdp1 might be a candidate prognostic marker of HCC.Depletion of Nrdp1 caused HCC cell proliferation,implicating that Nrdp1 may play an inhibitory role in regulating the proliferation of HCC cells.