title: Expression of hypoxia-inducible factor 1alpha gene affects the outcome in patients with ovarian cancer.
abstract: We conducted study to determine whether and how the expression of the hypoxia-inducible factor 1alpha (HIF-1alpha) gene relates to outcome in patients with epithelial ovarian cancer. A total of 66 patients with epithelial ovarian cancer, who underwent primary surgery followed by platinum-based chemotherapy, were entered into this study. We confirmed the expression of HIF-1alpha and the vascular endothelial growth factor (VEGF) by immunohistochemistry. To determine the quantity of HIF-1alpha and VEGF expression, messenger RNA of each gene was measured by real-time reverse transcription-polymerase chain reaction. The cutoff values were determined by the receiver-operating characteristic curve according to survival. The protein expressions of HIF-1alpha and VEGF were strongly observed in the cancer cells. The cutoff value of HIF-1alpha and VEGF gene expression was 6.0 and 3.0, respectively. The expression of HIF-1alpha did not relate to clinical stage, but tumor with low VEGF expression was observed more frequently in stage I patients. The response rate to chemotherapy did not differ between high and low expression of both genes. The overall survival for patients with high expression of HIF-1alpha was significantly lower, but disease-free survival did not differ between high and low expression of HIF-1alpha, whereas both overall and disease-free survival for patients with high expression of VEGF were significantly lower. Multivariate analysis revealed that FIGO stage and HIF-1alpha expression were independent prognostic factors but that VEGF was not. The present study suggested that the expression level of HIF-1alpha could be an independent prognostic factor in epithelial ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Tottori University, School of Medicine, Nishimachi, Yonago, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Shimogai
authors.forename: J
authors.initials: J
authors.lastname: Kigawa
authors.forename: H
authors.initials: H
authors.lastname: Itamochi
authors.forename: T
authors.initials: T
authors.lastname: Iba
authors.forename: Y
authors.initials: Y
authors.lastname: Kanamori
authors.forename: T
authors.initials: T
authors.lastname: Oishi
authors.forename: M
authors.initials: M
authors.lastname: Shimada
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: W
authors.initials: W
authors.lastname: Kawaguchi
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Terakawa
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010052:Ovariectomy / Q000379:methods; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A