title: Expression of miR-210 in relation to other measures of hypoxia and prediction of benefit from hypoxia modification in patients with bladder cancer.
abstract: BACKGROUND
  The addition of hypoxia modifiers carbogen and nicotinamide (CON) to radiotherapy (RT) improved overall survival (OS) in bladder cancer patients in the BCON phase III clinical trial. We investigate whether expression of hsa-miR-210 in BCON patient samples reflects hypoxia and predicts benefit from hypoxia modification.
  
  
  METHODS
  In all, 183 T1-T4a bladder cancer samples were available for miR-210 analysis. A total of 86 received RT+CON and 97 received RT alone. TaqMan qPCR plates were used to assess miR-210 expression. Patients were classified as low (<median expression) or high (⩾median) miR-210. Data on other hypoxia biomarkers were available for comparison.
  
  
  RESULTS
  Patients with high miR-210 had a trend towards improved 5-year OS with RT+CON (53.2%) compared with RT alone (37.8%; hazard ratio (HR) 1.68, 95% CI 0.95-2.95, P=0.07). No benefit was seen with low miR-210 (HR 1.02, 95% CI 0.58-1.79, P=0.97). High miR-210 was significantly associated with high HIF-1α protein (P=0.001), CA9 protein (P=0.0004), Glut-1 protein (P=0.001), 26-gene hypoxia score (P=0.007), tumour necrosis (P=0.02) and concurrent pTis (P=0.03).
  
  
  CONCLUSIONS
  High miR-210 may reflect hypoxia in bladder cancer. However, its ability to predict benefit from hypoxia modification does not improve upon other hypoxia markers. Investigation as part of a miRNA hypoxia signature may reveal the full potential of miR-210.
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Manchester M20 4BX, UK.
authors.forename: J J
authors.initials: JJ
authors.lastname: Irlam-Jones
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Manchester M20 4BX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Eustace
authors.affiliation: Department of Histopathology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
authors.forename: H
authors.initials: H
authors.lastname: Denley
authors.affiliation: Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Choudhury
authors.affiliation: Molecular Oncology Laboratories, Department of Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford OX3 9DS, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
authors.affiliation: Cancer Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hoskin
authors.affiliation: Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Centre, Manchester M20 4BX, UK.
authors.forename: C M L
authors.initials: CM
authors.lastname: West
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015687:Cell Hypoxia / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C543800:MIRN210 microRNA, human; D035683:MicroRNAs