Abstract LB-68: Comparative analysis of the miRNome in tumors and plasma from colorectal cancer patients

Abstract

Abstract MicroRNAs (miRNAs) constitute a recently discovered class of small cellular RNAs (typically 21-23 nt) that function as post-transcriptional regulators of gene expression through binding of miRNA target sequences in mRNA 3′ untranslated regions (UTRs). Current estimates indicate that at least one third of the cellular transcriptome is regulated by miRNAs, and that each miRNA has the potential to regulate hundreds of different mRNAs. As a consequence, miRNAs have been proposed to be master regulators of cellular state. This hypothesis has been borne out by a large number of studies demonstrating a causal link between miRNA dys-regulation and numerous disease states, including a diverse array of human cancers. Furthermore, the high relative stability of miRNA in common clinical source materials (e.g. FFPE blocks, plasma, urine, saliva, etc.) and the ability of miRNA expression profiles to accurately classify discrete tissue types and disease states have positioned miRNA quantification as a promising new tool for a wide range of diagnostic applications. To facilitate discovery and clinical transfer of miRNA-based diagnostic markers, we developed a genome-wide LNA™-based miRNA q-rt-PCR platform with unparalleled sensitivity and robustness. The platform uses a universal RT system and thus allows high-throughput profiling of miRNAs from important clinical sources without the need for pre-amplification. Using this system, we profiled samples relevant to colorectal cancer: tumor samples from colorectal cancer patients, normal adjacent tissue (NAT) from the same patients, plasma from the same patients from blood drawn on the day before surgery, and plasma from matched healthy volunteers. Both principal component analysis and unsupervised hierarchical clustering of the most variable miRNAs accurately classified tumor samples away from the set of NAT samples, suggesting that the single most important distinguishing factor between the two sets of samples is related to neoplastic transformation. We also define miRNAs that are differentially expressed in the plasma of healthy volunteers versus colorectal cancer patients and we will present an analysis of the overlap between differentially expressed miRNAs in plasma and tissue. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 LB-68.