title: mRNA expression levels of hypoxia-induced and stem cell-associated genes in human glioblastoma.
abstract: The roles of hypoxia-induced and stem cell-associated genes in the development of malignancy and tumour progression are well known. However, there are a limited number of studies analysing the impact of mRNA expression levels of hypoxia-induced and stem cell-associated genes in the tissues of brain tumours and glioblastoma patients. In this study, tumour tissues from patients with glioblastoma multiforme and tumour adjacent tissues were analysed. We investigated mRNA expression levels of hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), carbonic anhydrase 9 (CA9), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and osteopontin (OPN), and stem cell-associated genes survivin, epidermal growth factor receptor (EGFR), human telomerase reverse transcriptase (hTERT), Nanog and octamer binding transcription factor 4 (OCT4) using quantitative real-time polymerase chain reaction (qRT-PCR). Our data revealed higher mRNA expression levels of hypoxia-induced and stem cell-associated genes in tumour tissue than levels in the tumour adjacent tissues in patients with glioblastoma multiforme. A strong positive correlation between the mRNA expression levels of HIF-2α, CA9, VEGF, GLUT-1 and OPN suggests a specific hypoxia-associated profile of mRNA expression in glioblastoma multiforme. Additionally, the results indicate the role of stem-cell-related genes in tumour hypoxia. Kaplan-Maier analysis revealed that high mRNA expression levels of hypoxia-induced markers showed a trend towards shorter overall survival in glioblastoma patients (P=0.061). Our data suggest that mRNA expression levels of hypoxia-induced genes are important tumour markers in patients with glioblastoma multiforme.
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bache
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Swetlana
authors.initials: S
authors.lastname: Rot
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Keßler
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Güttler
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Henri
authors.initials: H
authors.lastname: Wichmann
authors.affiliation: Center for Reproductive Medicine and Andrology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Greither
authors.affiliation: Clinic of Urology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
authors.affiliation: Clinic of Urology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.affiliation: Department of Pediatrics, University of Göttingen, Göttingen, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Söling
authors.affiliation: Institute of Pathology, Eisleben, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Bilkenroth
authors.affiliation: Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vordermark
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D015687:Cell Hypoxia / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D053495:Osteopontin / Q000096:biosynthesis*; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D051272:Glucose Transporter Type 1; D009363:Neoplasm Proteins; D053495:Osteopontin; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1; C495677:SLC2A1 protein, human; C089226:CA9 protein, human