title: Coexpression of stemness factors Oct4 and Nanog predict liver resection.
abstract: BACKGROUND
  Oct4 and Nanog are two major transcription factors related to the stem cell self-renewal and differentiation. The aim of this study was to evaluate the correlation between these two stemness markers with recurrence, metastasis, and prognosis of hepatocellular carcinoma (HCC).
  
  
  METHODS
  Expression of Oct4 and Nanog was evaluated by immunohistochemistry in a random cohort of 228 HCC patients (cohort A), predominantly hepatitis B related, and validated in another independent cohort of 95 patients (cohort B). Survival analysis was performed by univariate and multivariate analyses. Oct4 and Nanog expression levels in 5 HCC cell lines with different metastatic potential were detected by Western blot assay and quantitative real-time PCR assay.
  
  
  RESULTS
  In tissue microarrays, coexpression of Oct4 and Nanog was dramatically associated with big tumor size (P = .001) and vascular invasion (P = .02) and was an independent predictor of postoperative recurrence (hazard ratio [HR] = 1.57, 95 % confidence interval [95 % CI] 1.21-2.04, P = .01) and poor prognosis (HR = 2.20, 95 % CI 1.71-2.88, P < .001). This association was further validated in patients in cohort B. Importantly, this correlation remained significant in patients with early-stage HCC or alpha-fetoprotein (AFP) negative HCC. In addition, expression of Oct4 and Nanog increased in a concordant manner with the increase of metastatic potential in human HCC cell lines.
  
  
  CONCLUSIONS
  Coexpression of stemness markers Oct4 and Nanog in HCC indicated the aggressive tumor behaviors and predicted a worse clinical outcome, which may be a useful biomarker to identify patients at high risk of postoperative recurrence.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yin
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Li
authors.forename: Bo-Heng
authors.initials: BH
authors.lastname: Zhang
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Ren
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yi
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000071317:Nanog Homeobox Protein; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D016016:Proportional Hazards Models; D015996:Survival Rate; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D000509:alpha-Fetoproteins