Abstract 4899: Small proline rich protein 3 (SPRR3) is a potential mediator of radiation resistance in HPV negative head and neck squamous cell carcinoma

Abstract

Abstract Purpose: Head and neck cancers (HNCs) are caused by two major etiologies that have significant prognostic significance: tobacco and human papillomavirus (HPV). Patients with HPV-positive HNC have significantly better outcomes than those with HPV-negative HNC. We have previously shown that this difference may be due, in part, to increased sensitivity to radiation in HPV-positive HNCs. In order to identify additional factors that may underlie differences in radiation sensitivity, we sought to understand radiation-induced changes in global gene expression between HPV-positive and HPV-negative HNCs. Methods: A panel of eight cell lines, four HPV positive (UD-SCC2, UM-SCC47, UPCI-SCC90, 93-VU-147T) and four HPV negative (SCC1, SCC6, SCC22B, SCC1483 were treated with radiation (4 Gy) or mock and total RNA isolated 4, 24, and 48 hrs after treatment. Global gene expression was analyzed using Affymetrix Gene 1.1 ST array chips. Comparisons between untreated, baseline control, and post-radiation expression were made using ArrayStar. Alterations in differentially expressed genes were validated by Real-Time quantitative PCR (RT-qPCR). Results: Out of the top 15 hits, several members of the small proline rich repeat (SPRR) family were identified. SPRR1A, SPRR1B, and SPRR3 were significantly upregulated in HPV negative as compared to HPV-positive cell lines. Differences in expression were validated using RT-qPCR in a panel of HNC cell lines. Conclusions: We identified changes in expression of SPRR3 in HPV negative cell lines. This gene is a member of a protein family known to scavenge reactive oxygen species. Its increased expression in HPV negative HNC may mediate resistance to radiation and contribute to the poor outcomes of patients in this cohort. SPRR3 is a potential novel molecular target that could improve the outcomes of patients with HPV negative HNC. Citation Format: Joshua A. Martin, Dana Gunderson, Randall J. Kimple. Small proline rich protein 3 (SPRR3) is a potential mediator of radiation resistance in HPV negative head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4899. doi:10.1158/1538-7445.AM2014-4899