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Open Access Research article

Stress associated gene expression in blood cells is related to outcome in radiotherapy treated head and neck cancer patients

Siv K Bøhn1, Kjell M Russnes2, Amrit K Sakhi1, Magne Thoresen3, Marit Holden4, JanØ Moskaug5, Mari C Myhrstad1, Ole K Olstad6, Sigbjørn Smeland27 and Rune Blomhoff12*

Author Affiliations

1 Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, 0316, Norway

2 Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Oslo, 0310, Norway

3 Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, 0316, Norway

4 Norwegian Computing Center, Oslo, 0314, Norway

5 Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, 0316, Norway

6 Department of Clinical Chemistry, Oslo University Hospital, Ullevål, Oslo, 0407, Norway

7 Institute for Clinical Medicine, University of Oslo, Oslo, 0316, Norway

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BMC Cancer 2012, 12:426  doi:10.1186/1471-2407-12-426

Published: 25 September 2012

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.

Trial registration

Raw data are available at ArrayExpress under accession number E-MEXP-2460.

Keywords:
Radiotherapy; HNSCC; Antioxidants; Microarray; GSEA; Cancer