Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
J Surg Oncol. 2012 Jan;105(1):71-80. doi: 10.1002/jso.22047. Epub 2011 Aug 3.
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.
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.
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.
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.
层粘连蛋白-2 是基底膜（BM）的普遍组成部分，肿瘤细胞会对其进行修饰，以促进肿瘤侵袭。然而，目前尚不清楚层粘连蛋白-2 在肝细胞癌（HCC）中的表达和功能。本研究旨在探讨层粘连蛋白-2 在 HCC 中的潜在作用。
通过免疫组织化学、免疫测定和实时 PCR 检测 HCC 组织、细胞系和血清中的层粘连蛋白-2 表达。使用强力霉素诱导和小干扰 RNA 分析来研究层粘连蛋白-2 表达的调节。
层粘连蛋白-2 在 HCC 组织和血清中均显著降低（P<0.001）。HCC 组织中层粘连蛋白-2 的低表达与肿瘤进展因子显著相关（P<0.05）。体外实验抑制基质金属蛋白酶（MMP）-9 可显著上调层粘连蛋白-2 的表达。此外，与良性肝病患者和正常志愿者相比，HCC 患者的血清层粘连蛋白-2 水平最低。此外，受试者工作特征曲线分析显示，层粘连蛋白-2 对 HCC 具有良好的诊断性能。
这些发现表明，层粘连蛋白-2 的表达降低可能在 HCC 的发展中具有潜在的发病作用，并且对 HCC 也可能具有潜在的诊断价值。
