Nuclear expression of WRAP53 beta is associated with a positive response to radiotherapy and improved overall survival in patients with head and neck squamous cell carcinoma

Garvin, Stina (author): Linköpings universitet,Östergötlands Läns Landsting,Klinisk patologi och klinisk genetik,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Öron- näsa- och halskliniken US

Tiefenböck, Katharina (author): Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Öron- näsa- och halskliniken US

Farnebo, Lovisa (author): Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Öron- näsa- och halskliniken US

Thunell, Lena (author): Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet

Roberg, Karin (author): Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Öron- näsa- och halskliniken US

(creator_code:org_t)

Elsevier, 2015
2015
English.
In: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 51:1, s. 24-30

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; http://kipublication...; show less...

Abstract Subject headings

Objectives: Today there are no reliable predictive markers for radiotherapy response in head and neck squamous cell carcinoma (HNSCC), leading to both under-and over-treatment of patients, personal suffering, and negative socioeconomic effects. Inherited mutation in WRAP53 beta (WD40 encoding RNA Antisense to p53), a protein involved in intracellular trafficking, dramatically increases the risk of developing HNSCC. The purpose of this study was to investigate whether WRAP53 beta can predict response to radiotherapy in patients with HNSCC. Materials and methods: Tumor biopsies from patients with HNSCC classified as responders or non-responders to radiotherapy were examined for the expression of the WRAP53 beta protein and single nucleotide polymorphisms in the corresponding gene employing immunohistochemistry and allelic discrimination, respectively. In addition, the effect of RNAi-mediated downregulation of WRAP53 beta on the intrinsic radiosensitivity of two HNSCC cell lines was assed using crystal violet and clonogenic assays. Results: Nuclear expression of WRAP53 beta was significantly associated with better response to radiotherapy and improved patient survival. Downregulation of WRAP53 beta with siRNA in vitro enhanced cellular resistance to radiation. Conclusions: Our findings suggest that nuclear expression of WRAP53 beta promotes tumor cell death in response to radiotherapy and is a promising predictor of radiotherapy response in patients with HNSCC.

By the author/editor: Garvin, Stina; Tiefenböck, Kath ...; Farnebo, Lovisa; Thunell, Lena; Farnebo, Mariann ...; Roberg, Karin

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Otorhinolaryngol ...

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