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

// Xian-Peng Li 1,* , Xiao-Yu Yang 2,* , Ewelina Biskup 3 , Jiang Zhou 1 , Hong-Liang Li 1 , Yi-Feng Wu 4 , Ming-Liang Chen 4 and Feng Xu 1 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.