Human Cancer Biology MicroRNA Alterations of Pancreatic Intraepithelial Neoplasias

Purpose:MicroRNA (miRNA) alterations are likely to contribute to the development of pancreatic cancer and may serve as markers for the early detection of pancreatic neoplasia. ExperimentalDesign: To identify themiRNA alterations that arise during the development of pancreatic cancer, we determined the levels of 735miRNAs in 34 pancreatic intraepithelial neoplasias (PanIN) and 15 normal pancreatic duct samples isolated by laser capture microdissection using TaqMan miRNA microarrays. Differential expression of selectedmiRNAs was confirmed by FISH analysis and by quantitative realtime reverse transcription PCR (qRT-PCR) analysis of selected candidate miRNAs in an independent set of PanIN and normal duct samples. Results: We identified 107 aberrantly expressed miRNAs in different PanIN grades compared with normal pancreatic duct samples and 35 aberrantly expressed miRNAs in PanIN-3 lesions compared with normal pancreatic duct samples. These differentially expressed miRNAs included those that have been previously identified as differentially expressed in pancreatic ductal adenocarcinomas (PDAC; including miR-21, miR-200a/b/c, miR-216a/b, miR-217, miR-146a, miR-155, miR-182, miR-196b, miR-203, miR222, miR-338-3p, miR-486-3p, etc.) as well as miRNAs not previously described as differentially expressed in these lesions (miR-125b,miR-296-5p,miR-183 ,miR-603,miR-625/ ,miR-708, etc.).miR-196bwas the most selectively differentially expressed miRNA in PanIN-3 lesions. Conclusions:ManymiRNAsundergo aberrant expression in PanIN lesions and are likely to be important in thedevelopmentofPDAC.ThemiRNAs, suchasmiR-196b,whoseexpression is limited toPanIN-3 lesions or pancreatic cancers could be useful as diagnostic markers. Clin Cancer Res; 18(4); 1–12. 2011 AACR.