MicroRNA analysis of fine-needle aspirates from pancreatic cancer.

Abstract

200 Background: Tissue-based research is a major challenge in localized pancreatic cancer (PC) especially those with locally advanced unresectable or borderline resectable disease. Approximately half of the patients are diagnosed by a fine needle aspirate (FNA) /biopsy of the pancreatic primary tumor with limited tissue available for correlative assays. Micro-RNAs (miRNAs) are biomarkers with the potential to be developed for prognostic and predictive purposes. Moreover, these molecules can facilitate the development of targeted therapies in PC. Methods: miRNA expression profiling and quantitative real-time PCR (qRT-PCR) were performed from RNA (25-100 ng per patient) extracted from formalin-embedded cell blocks (FFPE) obtained from diagnostic FNA of the pancreas. Expression profiles of miRNAs were compared to those from patients undergoing pancreatic biopsy for non-malignant conditions. Results: Cell blocks from FNAs from twenty-nine and 15 patients with pancreatic adenocarcinoma and non-malignant conditions were studied, respectively. miRNA profiling demonstrated deregulation of over 228 miRNA. The top 7 were validated by qRT-PCR. The expression of let-7c, let-7f, and miR-200c were significantly reduced in most patients. Conversely, the expression levels of miR-486-5p and miR-451 were significantly elevated. Significant interindividual variations were also noted in expression of certain miRNAs. Conclusions: FFPE obtained from diagnostic FNA of pancreatic tumor can be a valuable resource to study miRNA expression profiles of multiple miRNAs and undertake qRT-PCR in patients with localized PC and further supports the use of diagnostic FNA in RNA-based translational research. miRNA expression can be developed for use as prognostic and predictive biomarkers in future clinical trials in patients with PC.