title: Hypoxia-regulated MicroRNAs in Gastroesophageal Cancer.
abstract: OBJECTIVE
  The present study aimed to identify hypoxia-regulated microRNAs (HRMs) in vitro and investigate the clinical role of candidate HRMs in patients with gastroesophageal cancer (GEC).
  
  
  METHODS
  microRNA expression changes induced by hypoxia in human GEC cell lines were measured with microarrays and validated by quantitative real-time polymerase chain reaction. Candidate HRMs were measured in pre-therapeutic tumor samples from 195 patients with GEC.
  
  
  RESULTS
  Expression of miR-210 was shown to be significantly induced in esophageal squamous cell carcinoma (9.26-fold, p<0.001) and adenocarcinoma cell lines (4.95-fold, p<0.001) and miR-27a-star was significantly up-regulated in adenocarcinoma cell lines (4.79-fold, p=0.04). A weak but significant correlation between miR-210 expression and a 15-gene hypoxia signature was observed (Pearson r correlation: r=0.38, p<0.001). No significant associations of HRMs and clinical outcome in patients with GEC were identified.
  
  
  CONCLUSIONS
  This study supports the involvement of hypoxia on miRNAs in vitro and confirms the role of miR-210 as being a universal HRM.
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark mette@oncology.au.dk.
authors: Mette
authors: M
authors: Winther
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors: Jan
authors: J
authors: Alsner
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors: Brita Singers
authors: BS
authors: Sørensen
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors: Catja F
authors: CF
authors: Wittrup
authors: Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors: Trine
authors: T
authors: Tramm
authors: Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
authors: Lene
authors: L
authors: Baeksgaard
authors: Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
authors: Kenneth
authors: K
authors: Hofland
authors: Department of Oncology, Odense University Hospital, Odense, Denmark.
authors: Eva
authors: E
authors: Holtved
authors: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors: Marianne
authors: M
authors: Nordsmark
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: C543800:MIRN210 microRNA, human; D035683:MicroRNAs
keywords: Gastroesophageal cancer; hypoxia; miRNA-210; microRNAs