Oncotarget

Research Papers:

Co-expression of CXCL8 and HIF-1α is associated with metastasis and poor prognosis in hepatocellular carcinoma

Xian-Peng Li, Xiao-Yu Yang, Ewelina Biskup, Jiang Zhou, Hong-Liang Li, Yi-Feng Wu, Ming-Liang Chen and Feng Xu _

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Oncotarget. 2015; 6:22880-22889. https://doi.org/10.18632/oncotarget.4412

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Abstract

Xian-Peng Li1,*, Xiao-Yu Yang2,*, Ewelina Biskup3, Jiang Zhou1, Hong-Liang Li1, Yi-Feng Wu4, Ming-Liang Chen4 and Feng Xu1

1 Division of Gastroenterology and Hepatology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China

2 Division of Special Treatment II, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

3 Department of Oncology, University Hospital of Basel, Basel, Switzerland

4 Division of Hepatobiliary Surgery, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China

* These authors contributed equally to this study and should be considered as co-first authors

Correspondence to:

Feng Xu, email:

Keywords: IL-8, cytokines, migration, hypoxia, metastasis, HCC

Received: February 04, 2015 Accepted: May 25, 2015 Published: June 10, 2015

Abstract

Hypoxia inducible factor-1α (HIF-1α), induces cytokines such as CXCL8 and tumor dissemination, chemo- and radio-resistance. We analyzed correlation between HIF-1α and CXCL8 levels, tumor characteristics and overall survival in 102 hepatocellular carcinoma (HCC) patients. Levels of HIF-1α and CXCL8 were increased in HCC tissues and cell lines. Patients with high levels of HIF-1α and CXCL8 had worse outcome and poorer prognosis than those with lower levels. Co-overexpression of HIF-1α and CXCL8 was an independent negative prognostic factor for overall and disease-free survival. HIF-1α silencing and CXCL8 siRNA decreased migration under hypoxic conditions in vitro. Hypoxia-induced activation of AKT/mTOR/STAT3 pathways was reversed by depletion of CXCL8. We conclude that HIF-1α and CXCL8 induce HCC progression and metastasis, associated with activation of AKT/mTOR/STAT3. Co-expression of HIF-1α and CXCL8 is a prognostic marker and a potential therapeutic target in HCC.


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