Jennifer Permuth-Wey, Y Ann Chen, Kate Fisher, Susan McCarthy, Xiaotao Qu, Mark C Lloyd, Agnieszka Kasprzak, Michelle Fournier, Vonetta L Williams, Kavita M Ghia, Sean J Yoder, Laura Hall, Christina Georgeades, Funmilayo Olaoye, Kazim Husain, Gregory M Springett, Dung-Tsa Chen, Timothy Yeatman, Barbara Ann Centeno, Jason Klapman, Domenico Coppola, and Mokenge Malafa
BACKGROUND:Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic ductal adenocarcinoma (PDAC) precursors. Differentiating between high-risk IPMNs that warrant surgical resection and low-risk IPMNs that can be monitored is a significant clinical problem, and we sought to discover a panel of mi(cro)RNAs that accurately classify IPMN risk status. METHODOLOGY/PRINCIPAL FINDINGS:In a discovery phase, genome-wide miRNA expression profiling was performed on 28 surgically-resected, pathologically-confirmed IPMNs (19 high-risk, 9 low-risk) using Taqman MicroRNA Arrays. A validation phase was performed in 21 independent IPMNs (13 high-risk, 8 low-risk). We also explored associations between miRNA expression level and various clinical and pathological factors and examined genes and pathways regulated by the identified miRNAs by integrating data from bioinformatic analyses and microarray analysis of miRNA gene targets. Six miRNAs (miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-130a) were down-regulated in high-risk versus low-risk IPMNs and distinguished between groups (P