Clinical significance of decreased nidogen‐2 expression in the tumor tissue and serum of patients with hepatocellular carcinoma

Abstract

Background and Objectives Nidogen‐2 is a ubiquitous component of basement membrane (BM), which is modified by tumor cells to facilitate tumor invasion. However, the expression and function of nidogen‐2 in hepatocellular carcinoma (HCC) remains unknown at present. In this study, we sought to investigate the potential role of nidogen‐2 in HCC. Methods Nidogen‐2 expression in HCC tissues, cell lines, and serum was evaluated by immunohistochemistry, immunoassay, and real‐time PCR assays. The regulation of nidogen‐2 expression was investigated using doxycycline induction and small interfering RNA analyses. Results Nidogen‐2 was significantly decreased in both HCC tissues and serum (P < 0.001). The decreased expression of nidogen‐2 in HCC tissues was significantly correlated with tumor progression factors (P < 0.05). Inhibition of matrix metalloproteinase (MMP)‐9 led to significantly upregulate nidogen‐2 expression in vitro assays. Moreover, patients with HCC had lowest serum nidogen‐2 levels compared with patients with benign liver diseases and normal volunteers. Furthermore, the receiver operating characteristic curve analysis revealed a good diagnostic performance of nidogen‐2 for HCC. Conclusions These findings suggest that decreased expression of nidogen‐2 may have a potential pathogenetic role in the development of HCC and may also have potential diagnostic value for HCC. J. Surg. Oncol. 2012; 105:71–80.