Abstract 1166: Upregulation of microRNAs in colorectal tumors and association with disease stage.

Introduction MicroRNAs (miRNAs) are small, noncoding RNAs that function as regulators of many critical cellular processes. Increased expression of specific microRNAs in tumor tissue may be indicative of a patient9s prognosis. The purpose of this study was to assess miRNA upregulation in fresh frozen colorectal cancer (CRC) tumors compared to paired normal colorectal tissue in a prospective cohort of CRC patients. Methods Tumor and normal tissue were collected at the time of surgery from 40 stage I-IV CRC patients participating in the ColoCare Study in Seattle, WA. The Qiagen miRNeasy kit was used to isolate miRNAs for analysis. Expression of candidate miRNAs (e.g., miR-141, miR-31, miR-29a, mir-92a, miR-203) was measured using Taqman qRT-PCR with miRNA-specific stem loop primers. For each miRNA, copy number was determined via standard curves and normalized to miR-16 expression for each sample. Expression in tumor was compared to expression in paired normal tissue for each participant. In addition, we profiled two stage III CRC tumor-normal pairs using the miCURY LNA human panel I qRT-PCR array from Exiqon. Relative expression from the Exiqon panel was calculated using GenEx software and endogenous control assays. The Wilcoxon two sample test was used to compare normalized miRNA upregulation between groups. Results Expression of miR-31 was greater than 10-fold higher in tumor compared to normal tissue for 13 of 38 tumor-normal pairs with Taqman data available. Overexpression of miR-31 in tumor tissue was significantly correlated with stage III-IV CRC when compared to stage I-II CRC (p Conclusion In this study, upregulation of miR-31 in CRC tumor tissue was associated with more advanced disease stage in CRC patients. Future studies will investigate additional miRNAs, and associations with clinicopathological features, patient outcomes, and circulating miRNA levels. Citation Format: Karen W. Makar, Michelle A. Wurscher, Nina Habermann, William M. Grady, Cornelia M. Ulrich. Upregulation of microRNAs in colorectal tumors and association with disease stage. [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 1166. doi:10.1158/1538-7445.AM2013-1166