title: Reduced N-cadherin expression is associated with metastatic potential and poor surgical outcomes of hepatocellular carcinoma.
abstract: OBJECTIVE
  N-cadherin (N-cad), one of the classic cadherins, has been reported to be involved in tumor metastasis in some types of tumors. This study aims to investigate the expression status of N-cad in hepatocellular carcinoma (HCC) and the correlation between N-cad expression and metastatic potential, as well as the surgical outcomes of HCC.
  
  
  METHODS
  N-cad expression in HCC and adjacent liver tissues, as well as normal liver tissues, was studied by immunohistochemistry and Western blot, and the relationship between N-cad expression and the clinicopathological features of HCC was evaluated. By using RNA interference technique, the correlation of N-cad expression and metastatic potential was investigated by downregulating N-cad expression in HCCLM3 cells, and the effects of N-cad downregulation on cell aggregation, migration, and invasion were then analyzed. Furthermore, the correlation between N-cad expression and the surgical outcomes of a cohort of HCC patients was analyzed.
  
  
  RESULTS
  In liver tissues, N-cad was strongly expressed on cell-cell boundaries, whereas various reduced-expression patterns were observed in tumors. Of 64 HCC, 34 (53%) tumors showed reduced N-cad expression, compared with their adjacent liver tissues. The decreased expression of N-cad was significantly correlated with poorer tumor differentiation (P = 0.001) and vascular invasion (P = 0.003). N-cad knockdown in HCCLM3 cells resulted in decreased cell aggregation and increased cell migration and invasion. The decreased expression of N-cad in HCC was significantly associated with shorter postoperative disease-free survival (P = 0.039).
  
  
  CONCLUSIONS
  N-cad expression is decreased in HCC, and the downregulation of N-cad is associated with the metastatic potential of HCC and poorer surgical prognosis.
authors.affiliation: Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Da-Qian
authors.initials: DQ
authors.lastname: Zhan
authors.forename: Shuang
authors.initials: S
authors.lastname: Wei
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.forename: Bin-Yong
authors.initials: BY
authors.lastname: Liang
authors.forename: Gui-Bao
authors.initials: GB
authors.lastname: Ji
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Xiong
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D016009:Chi-Square Distribution; D002681:China; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C050361:CDH2 protein, human; D015820:Cadherins