title: Clinical significance of decreased nidogen-2 expression in the tumor tissue and serum of patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Cheng
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Huang
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Chen
authors.forename: Long-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D061965:Matrix Metalloproteinase Inhibitors; C114729:NID2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9