Annals of Surgical Oncology

, Volume 19, Issue 9, pp 2877–2887

Coexpression of Stemness Factors Oct4 and Nanog Predict Liver Resection

Authors

  • Xin Yin
    • Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education
  • Yi-Wei Li
    • Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education
    • Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education
  • Zheng-Gang Ren
    • Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education
  • Shuang-Jian Qiu
    • Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education
  • Yong Yi
    • Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education
  • Jia Fan
    • Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education
Hepatobiliary Tumors

DOI: 10.1245/s10434-012-2314-6

Cite this article as:
Yin, X., Li, Y., Zhang, B. et al. Ann Surg Oncol (2012) 19: 2877. doi:10.1245/s10434-012-2314-6
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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.

Supplementary material

10434_2012_2314_MOESM1_ESM.doc (34 kb)
Supplementary material 1 (DOC 34 kb)
10434_2012_2314_MOESM2_ESM.doc (48 kb)
Supplementary material 2 (DOC 48 kb)

Copyright information

© Society of Surgical Oncology 2012