title: Stress associated gene expression in blood cells is related to outcome in radiotherapy treated head and neck cancer patients.
abstract: BACKGROUND
  We previously observed that a radiotherapy-induced biochemical response in plasma was associated with favourable outcome in head and neck squamous carcinoma cancer (HNSCC) patients. The aim of the present study was to compare stress associated blood cell gene expression between two sub-groups of HNSCC patients with different biochemical responses to radiotherapy.
  
  
  METHODS
  Out of 87 patients (histologically verified), 10 biochemical 'responders' having a high relative increase in plasma oxidative damage and a concomitant decrease in plasma antioxidants during radiotherapy and 10 'poor-responders' were selected for gene-expression analysis and compared using gene set enrichment analysis.
  
  
  RESULTS
  There was a significant induction of stress-relevant gene-sets in the responders following radiotherapy compared to the poor-responders. The relevance of the involvement of similar stress associated gene expression for HNSCC cancer and radioresistance was verified using two publicly available data sets of 42 HNSCC cases and 14 controls (GEO GSE6791), and radiation resistant and radiation sensitive HNSCC xenografts (E-GEOD-9716).
  
  
  CONCLUSIONS
  Radiotherapy induces a systemic stress response, as revealed by induction of stress relevant gene expression in blood cells, which is associated to favourable outcome in a cohort of 87 HNSCC patients. Whether these changes in gene expression reflects a systemic effect or are biomarkers of the tumour micro-environmental status needs further study.
  
  
  BACKGROUND
  Raw data are available at ArrayExpress under accession number E-MEXP-2460.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo 0316, Norway.
authors.forename: Siv K
authors.initials: SK
authors.lastname: Bøhn
authors.forename: Kjell M
authors.initials: KM
authors.lastname: Russnes
authors.forename: Amrit K
authors.initials: AK
authors.lastname: Sakhi
authors.forename: Magne
authors.initials: M
authors.lastname: Thoresen
authors.forename: Marit
authors.initials: M
authors.lastname: Holden
authors.forename: Jan Ø
authors.initials: JØ
authors.lastname: Moskaug
authors.forename: Mari C
authors.initials: MC
authors.lastname: Myhrstad
authors.forename: Ole K
authors.initials: OK
authors.lastname: Olstad
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Smeland
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001499:Bayes Theorem; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006258:Head and Neck Neoplasms / Q000097:blood / Q000235:genetics* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D014408:Biomarkers, Tumor