title: A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma.
abstract: BACKGROUND
  For decades, tumour hypoxia has been pursued as a cancer treatment target. However, prognostic and predictive biomarkers are essential for the use of this target in the clinic. This study investigates the prognostic value of a hypoxia-induced gene profile in localised soft tissue sarcoma (STS).
  
  
  METHODS
  The hypoxia-induced gene quantification was performed by real-time quantitative PCR (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene expression cut-points were determined in a test cohort of 55 STS patients and used to allocate each patient into a more or a less hypoxic group. The cut-points found in the test cohort were applied to a cohort of 77 STS patients for validation.
  
  
  RESULTS
  For patients with localised high-grade STS treated with surgery with or without postoperative radiation therapy, the prognostic value of the hypoxia-induced gene profile was proved in the test cohort and confirmed in the validation cohort. After adjustment for confounders, the hazard ratio (HR) was 3.2 (95% CI: 1.5; 7.0) for patients with more hypoxic tumours compared with patients with less hypoxic tumours regarding disease-specific survival. Moreover, for the development of metastatic disease, the HR was 2.61 (95% CI: 1.27; 5.33).
  
  
  CONCLUSIONS
  The hypoxia-induced gene profile is a validated independent prognostic marker that may help identify STS patients needing more aggressive or different adjuvant treatment.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
authors.forename: Ninna
authors.initials: N
authors.lastname: Aggerholm-Pedersen
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
authors.forename: Brita Singers
authors.initials: BS
authors.lastname: Sørensen
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
authors.affiliation: Department of Oncology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
authors.forename: Kasper
authors.initials: K
authors.lastname: Toustrup
authors.affiliation: Department of Pathology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Baerentzen
authors.affiliation: Faculty of Health, Aarhus University, Nordre Ringgade 1, Aarhus C 8000, Denmark.
authors.forename: Ole Steen
authors.initials: OS
authors.lastname: Nielsen
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
authors.forename: Katja
authors.initials: K
authors.lastname: Maretty-Kongstad
authors.affiliation: Department of Oncology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Nordsmark
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Alsner
authors.affiliation: Department of Oncology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
authors.forename: Akmal
authors.initials: A
authors.lastname: Safwat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D012509:Sarcoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D059467:Transcriptome; D000072258:Tumor Hypoxia / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor