title: Co-expression of CXCL8 and HIF-1α is associated with metastasis and poor prognosis in hepatocellular carcinoma.
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.
authors.affiliation: Division of Gastroenterology and Hepatology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China.
authors.forename: Xian-Peng
authors.initials: XP
authors.lastname: Li
authors.affiliation: Division of Special Treatment II, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Department of Oncology, University Hospital of Basel, Basel, Switzerland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Biskup
authors.affiliation: Division of Gastroenterology and Hepatology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Division of Gastroenterology and Hepatology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Li
authors.affiliation: Division of Hepatobiliary Surgery, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Wu
authors.affiliation: Division of Hepatobiliary Surgery, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China.
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology and Hepatology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018572:Disease-Free Survival; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: C508606:CXCL8 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016209:Interleukin-8; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: HCC; IL-8; cytokines; hypoxia; metastasis; migration