Abstract 3162: Characterizing premalignant progression within optically altered oral mucosa fields using microRNA expression profiles

Abstract

Abstract BACKGROUND: Oral cancer is one of the most commonly diagnosed malignancies worldwide, with a dismal 5-year survival rate that has not changed for decades. An improved understanding of the molecular basis of oral cancer, particularly the alterations contributing to the non-invasive disease stages, is essential for developing novel strategies for diagnosis, predicting prognosis and establishing effective therapeutics. To date, the role of microRNAs (miRNAs), a class of short, non-coding, single stranded RNAs that negatively regulate gene expression, in oral tumorigenesis - and oral premalignant lesions (OPLs) specifically, is largely unknown. The objective of this study is to identify miRNAs that are deregulated in OPLs and to elucidate their impact on disease initiation and progression. METHODS: MiRNA expression is tissue-specific and can be influenced by a number of extrinsic factors, such as smoking and diet. To remove variation due to timing differences in sampling, we analyzed histologically different OPL and normal tissue biopsies taken at the same time from a single, contiguous field in a patient's mouth. For each of the 10 patient cases, we obtained microdissected tissues from normal, dysplastic and carcinoma in situ lesions. Diseased regions in the oral cavity were detected by a hand-held Fluorescence Visualization (FV) device capable of delineating occult disease proximal to oral tumors in real-time. Total RNA was isolated from each microdissected specimen and profiled for the expression of 742 human miRNAs using miRCURY LNA™ Universal RT microRNA PCR. Data were normalized based on the manufacturer guidelines and a minimum of 2-fold expression change relative to the matched normal was used to define candidate miRNAs. RESULTS: Overall, a greater amount of miRNA alterations were present in the more advanced lesions, suggesting that miRNA changes are accumulated during premalignant progression. In addition, we have identified several candidate miRNAs that were consistently deregulated at the earliest stages of oral cancer development, with miR-21 and miR-375 being the most frequently up-regulated and down-regulated miRNAs, respectively. Examining the individual expression profiles of these candidates across sequential OPLs, we also found that they follow distinct patterns of deregulation overtime. Each of these miRNAs may therefore function differently in oral tumorigenesis and be of different clinical significance when deregulated. CONCLUSIONS: This is a unique sample set that allows us to examine intralesional progression within a single surgical field and delineate the key miRNA aberrations driving this process. Ultimately, our data will aid in the development of a novel genomic platform for risk assessment, diagnosis and potential targeted therapies that may lead to improved disease management. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3162. doi:1538-7445.AM2012-3162