Abstract 1949: The identification of potentially prognostic microRNAs in human nasopharyngeal carcinoma.

Abstract

Abstract Purpose/Objective: The majority of nasopharyngeal carcinoma (NPC) patients undergo curative radiation therapy (RT), with concurrent chemotherapy (CT) in cases of locally advanced disease. Current treatments achieve a modest 5-year overall survival rate of ∼70%, underscoring the need for a better understanding of NPC biology in order to develop novel tools to target this disease. In recent years, it has become apparent that micro-RNAs (miRNAs) play important roles in many, if not all human malignancies. Furthermore, miRNAs have been identified whose expression is capable of predicting patient outcome in a variety of human cancers; hence, we proceed to address the primary hypothesis that there is a miRNA expression signature capable of predicting outcome for NPC patients. Materials/Methods: The expression level of 734 unique human and viral miRNAs in 121 fully clinically-annotated NPC samples plus 10 normal nasopharyngeal epithelial tissues from healthy individuals was analyzed using the nCounter human microRNA panel from Nanostring®. These data were analyzed in relation to patient clinical and outcomes data (median follow-up time was 6.9 years), in order to identify associations between individual and combinations of miRNAs with clinical parameters. Results: Global miRNA expression analyses identified 49 miRNAs which were differentially-expressed between NPC and normal nasopharyngeal epithelial tissues. Using a 2-fold cut-off and Bonferroni correction for multiple comparisons, 39 miRNAs were significantly over-expressed and 10 were significantly under-expressed (miR-145, -216a, -100, -423, -424, -99b, -125a, -125b, -30c, -200a). Additionally, the expression level of 21 miRNAs, appeared to be strongly associate with clinical outcome. Specifically, there were two under-expressed miRNAs which were able to classify patients into low, medium, or high risk groups for distant relapse, wherein their 5-year distant relapse rates were: 0%, 10%, and 36%, respectively; p=0.0006). Conclusions: These preliminary data suggest a potential miRNA signature set which can predict for distant relapse, the major cause of death in NPC given the excellent loco-regional control rates with the use of IMRT. Our next step will be to measure the expression level of these 21 candidate miRNAs in an independent validation set of 131 NPC patients to confirm whether any of these miRNAs indeed have prognostic value in NPC. Biological insights will also be acquired by evaluating these miRNAs in pre-clinical NPC models. Prognostic signatures acquired could be used to categorize risk groups, and also facilitate the discovery and development of novel molecularly-targeted therapies which could improve outcome for future NPC patients. Citation Format: Jeff Bruce, Angela Hui, Daryl Waggot, Bayardo Perez-Ordonez, Ilan Weinreb, Wei Xu, Fei-Fei Liu. The identification of potentially prognostic microRNAs in human nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1949. doi:10.1158/1538-7445.AM2013-1949