title: Cancer stem cell markers correlate with early recurrence and survival in hepatocellular carcinoma.
abstract: OBJECTIVE
  To investigate whether expression of cancer stem cell (CSC) markers is associated with recurrence and survival in hepatocellular carcinoma (HCC) patients.
  
  
  METHODS
  A consecutive series of 90 HCC patients who underwent curative hepatectomy between April 2007 and April 2009 were analyzed. Of the 90 patients, 38 (42%) experienced recurrence within two years of surgery. To adjust for baseline differences between this early recurrence group and the other patients, propensity-score matching was used to generate 25 pairs of patients. Immunohistochemistry was used to compare expression of CD133, CD90, and epithelial cell adhesion molecule (EpCAM) in liver tissues from propensity score-matched patients and from 10 healthy adults. Associations of the three markers with HCC, clinicopathological characteristics, early recurrence, and survival time were explored.
  
  
  RESULTS
  The expression of all three CSC markers was significantly higher in HCC tissue than in healthy liver tissue (P < 0.001 for all). Among the HCC clinicopathology characteristics examined, the absence of tumor capsule was associated with CD133 expression (P = 0.005); higher histopathology grade and larger tumor size were associated with CD90 expression (P = 0.010 and 0.034, respectively); and elevated serum alpha-fetoprotein levels were associated with EpCAM expression (P = 0.021). Expression of CD90 and EpCAM was significantly higher in the early recurrence group than in other patients (P = 0.001 and 0.045, respectively), whereas CD133 expression was not significantly different between the two groups (P = 0.440). Multivariate analysis identified only CD90 expression as significantly associated with early recurrence. Log-rank analysis identified expression of both CD90 and EpCAM as significantly associated with survival time of HCC patients. Cox regression identified EpCAM expression as an independent predictor of survival time.
  
  
  CONCLUSIONS
  Expression of CD133, CD90, and EpCAM CSC markers may be linked to HCC tumor onset and/or progression. In addition, EpCAM expression is associated with shorter survival time, while CD90 expression is associated with early HCC recurrence.
authors.affiliation: Zhe Guo, Le-Qun Li, Jing-Hang Jiang, Bang-De Xiang, Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Zhe Guo, Le-Qun Li, Jing-Hang Jiang, Bang-De Xiang, Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Le-Qun
authors.initials: LQ
authors.lastname: Li
authors.affiliation: Zhe Guo, Le-Qun Li, Jing-Hang Jiang, Bang-De Xiang, Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Jing-Hang
authors.initials: JH
authors.lastname: Jiang
authors.affiliation: Zhe Guo, Le-Qun Li, Jing-Hang Jiang, Bang-De Xiang, Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ou
authors.affiliation: Zhe Guo, Le-Qun Li, Jing-Hang Jiang, Bang-De Xiang, Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Zeng
authors.affiliation: Zhe Guo, Le-Qun Li, Jing-Hang Jiang, Bang-De Xiang, Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Bang-De
authors.initials: BD
authors.lastname: Xiang
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D000071858:Epithelial Cell Adhesion Molecule; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000378:metabolism; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010455:Peptides / Q000378:metabolism; D011379:Prognosis; D018800:Thy-1 Antigens / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D018800:Thy-1 Antigens
keywords: CD133; CD90; Cancer stem cells; Epithelial cell adhesion molecule; Hepatocellular carcinoma