Journal
JOURNAL OF SURGICAL ONCOLOGY
Volume 105, Issue 1, Pages 71-80Publisher
WILEY
DOI: 10.1002/jso.22047
Keywords
nidogen-2; hepatocellular carcinoma; matrix metalloproteinase; tissue microarray; biomarker
Funding
- National Natural Science Foundation of China [81071871]
- Natural Science Foundation of Guangdong Province (China) [10451008901006014]
- Science and Technology Planning Project of Guangdong Province (China) [2009B030801014]
- Department of Surgical Laboratory at the First Affiliated Hospital of Sun Yat-Sen University
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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. (C) 2011 Wiley Periodicals, Inc.
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