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01.09.2012 | Hepatobiliary Tumors | Ausgabe 9/2012

Annals of Surgical Oncology 9/2012

Coexpression of Stemness Factors Oct4 and Nanog Predict Liver Resection

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 9/2012
Autoren:
MD Xin Yin, MD Yi-Wei Li, MD Bo-Heng Zhang, MD Zheng-Gang Ren, MD Shuang-Jian Qiu, MD Yong Yi, MD, PhD Jia Fan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1245/​s10434-012-2314-6) contains supplementary material, which is available to authorized users.
X. Yin and Y.-W. Li contributed equally to this work.

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.

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