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Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients
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- Farnebo, Lovisa (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Oto-Rhino-Laryngologi,Hälsouniversitetet,Öron- näsa- och halskliniken US
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- Tiefenböck, Katharina (författare)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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- Ansell, Anna (författare)
- Linköpings universitet,Avdelningen för neurovetenskap,Hälsouniversitetet
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- (creator_code:org_t)
- 2013-05-09
- 2013
- Engelska.
- Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 133:8, s. 1994-2003
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Head and neck squamous cell carcinoma (HNSCC) is a malignancy that is associated with severe mortality despite advances in therapy. Todays standard treatment most commonly includes radiotherapy, often combined with chemotherapy or surgery. There are so far no established biomarkers to predict response to radiation, and thus the aim of this study was to investigate a series of markers that could potentially identify HNSCC patients who would benefit from radiotherapy. The selected markers, both proteins (epidermal growth factor receptor, survivin and p53), and single nucleotide polymorphisms (SNPs) in the genes of XRCC3, XRCC1, XPC, XPD, MDM2, p53 and FGFR4 were correlated to the response to radiotherapy and overall survival. Investigations were performed on pretreatment tumor biopsies from patients classified as responders or nonresponders to radiotherapy. Protein expression was examined using immunohistochemistry and the genotyping of specific SNPs was analyzed using PCR-RFLP or pyrosequencing. We found that survivin expression was significantly stronger in the responder group (p = 0.003) and that patients with a strong survivin expression had a significantly better overall survival (p andlt; 0.001). Moreover, downregulation of survivin by siRNA in two HNSCC cell lines significantly decreased their sensitivity to radiation. Among the SNPs analyzed, patients with the XPD Lys751Gln SNP had a significantly shorter overall survival (p = 0.048), and patients with the FGFR4 Gly388Arg SNP had a significantly longer overall survival (p = 0.010). In conclusion, our results suggest that survivin plays an important role in the response to radiotherapy and may be a useful marker for predicting radiotherapy response in patients with HNSCC. less thanbrgreater than less thanbrgreater thanWhats new? Resistance to radiation therapy is a significant problem in the treatment of head and neck squamous cell carcinoma (HNSCC) and has created a need for the discovery of markers predictive of radiotherapy response. One promising marker is survivin, an inhibitor of apoptosis. Here, in pre-treatment biopsies from 40 patients with HNSCC, strong survivin expression was significantly associated with response to radiotherapy and increased overall survival. The data also indicate that single nucleotide polymorphisms in the genes XPD and FGFR4 are other possible predictors of overall survival after radiotherapy.
Nyckelord
- head and neck tumors
- radiotherapy
- survivin
- single nucleotide polymorphism
- MEDICINE
- MEDICIN
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- ref (ämneskategori)
- art (ämneskategori)
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- Farnebo, Lovisa
- Tiefenböck, Kath ...
- Ansell, Anna
- Thunell, Lena
- Garvin, Stina
- Roberg, Karin
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- Linköpings universitet
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