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
2015 (English)In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 51, no 1, 24-30 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Elsevier , 2015. Vol. 51, no 1, 24-30 p.
Head and neck cancer; Radiotherapy; Predictive factors; Survivin; WRAP53
Cancer and Oncology Otorhinolaryngology
IdentifiersURN: urn:nbn:se:liu:diva-113161DOI: 10.1016/j.oraloncology.2014.10.003ISI: 000346210900007PubMedID: 25456005OAI: oai:DiVA.org:liu-113161DiVA: diva2:780374
Funding Agencies|Swedish Laryng Foundation; Ake Wiberg Foundation; Swedish Cancer Society [2008/552, 2010/545]; County Council of Ostergotland; Research Funds of Linkoping University Hospital2015-01-142015-01-122016-04-24