Abstract 3052: MicroRNA as a potential diagnostic marker for oral squamous cell carcinoma

Abstract

Abstract MicroRNAs (miRNAs), a group of small non-coding RNAs, regulate post transcriptional gene expression by binding to their target messenger RNAs resulting in their degradation or reduced translation. Evidence suggests that miRNAs are involved in the pathogenesis of cancer and could potentially be used as diagnostic or prognostic markers. MicroRNAs have been studied extensively in solid tumors such as breast, lung and colon cancers; however, there are few studies of miRNA in oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate the potential role of miRNA in OSCC. We selected tumors from 40 patients with OSCC (10 HPV-positive oral cavity tumors, 10 HPV-negative oral cavity tumors, 10 HPV-positive oropharyngeal tumors, and 10 HPV-negative oropharyngeal tumors) and normal oral tissues from 10 patients without cancer (all HPV-negative) who were treated at three University of Washington affiliated medical centers between December 2003 and April 2007 and were enrolled in the study with informed consent. The tissues were obtained at the time of surgery and DNA and RNA were simultaneously extracted using TRIzol method (Invitrogen, Carlsbad, CA). RNA was tested using miRCURY LNATM microRNA v.11.0 (Exiqon, Vedbaek, Denmark). This array covers 1,282 mature human miRNAs and 80 viral miRNAs. Using TIGR software and significance analysis of microarrays (SAM) and a cut point of 2-fold change, we found 30 miRNAs (12 up-regulated and 18 down-regulated) differentially expressed between OSCC and controls. We found no difference in miRNA expression between HPV-positive and HPV-negative tumors, both overall and among oropharyngeal tumors. To confirm the Exiqon array results, we conducted qRT-PCR of miRNAs that had >4-fold change (miR-223: 6.2-fold; miR-21: 4.5-fold); the correlation between miRNA expression as measured by Exiqon array and qRT-PCR was 0.63 (p<0.001) for miR-223 and 0.64 (p<0.001) for miR-21. In linear regression analyses adjusting for age and sex in an independent set of 121 OSCC cancers and 30 normal oral tissue from controls, the difference in mean Ct value between cases and controls was 2.7 (CI, 1.6 to 3.8), p<0.001 and 2.9 (CI, 2.4 to 3.4), p<0.001 for miR-223 and miR-21, respectively. To evaluate whether expression of miR-223 and miR-21 were associated with overall and OSCC-specific survival, we performed Cox proportional hazards regression adjusted for age and sex on 161 cases with a median of 36 months of follow-up. We observed no difference in overall survival associated with increasing level of miR-223 expression (HR=1.0; CI, 0.9-1.1) or miR21 expression (HR=1.0; CI, 0.8-1.2). Results were similar for OSCC-specific survival. In conclusion, our results show that a number of miRNAs are differentially expressed between OSCC and normal oral tissue. These deregulated miRNAs may serve as novel diagnostic markers for OSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3052.