title: Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide, partly because methods are lacking to detect disease at an early, operable stage. Noninvasive PDAC precursors called intraductal papillary mucinous neoplasms (IPMN) exist, and strategies are needed to aid in their proper diagnosis and management. Data support the importance of miRNAs in the progression of IPMNs to malignancy, and we hypothesized that miRNAs may be shed from IPMN tissues and detected in blood. Our primary goals were to measure the abundance of miRNAs in archived preoperative plasma from individuals with pathologically confirmed IPMNs and healthy controls and discover plasma miRNAs that distinguish between IPMN patients and controls and between "malignant" and "benign" IPMNs. Using novel nCounter technology to evaluate 800 miRNAs, we showed that a 30-miRNA signature distinguished 42 IPMN cases from 24 controls [area underneath the curve (AUC) = 74.4; 95% confidence interval (CI), 62.3-86.5, P = 0.002]. The signature contained novel miRNAs and miRNAs previously implicated in pancreatic carcinogenesis that had 2- to 4-fold higher expression in cases than controls. We also generated a 5-miRNA signature that discriminated between 21 malignant (high-grade dysplasia and invasive carcinoma) and 21 benign (low- and moderate-grade dysplasia) IPMNs (AUC = 73.2; 95% CI, 57.6-73.2, P = 0.005), and showed that paired plasma and tissue samples from patients with IPMNs can have distinct miRNA expression profiles. This study suggests feasibility of using new cost-effective technology to develop a miRNA-based blood test to aid in the preoperative identification of malignant IPMNs that warrant resection while sparing individuals with benign IPMNs the morbidity associated with overtreatment.
authors: Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida. Department of Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida. jenny.wey@moffitt.org.
authors: Jennifer
authors: J
authors: Permuth-Wey
authors: Departments of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Dung-Tsa
authors: DT
authors: Chen
authors: Departments of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: William J
authors: WJ
authors: Fulp
authors: Department of Molecular Genomics, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Sean J
authors: SJ
authors: Yoder
authors: Departments of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Yonghong
authors: Y
authors: Zhang
authors: Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida. Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors: Christina
authors: C
authors: Georgeades
authors: Department of Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Kazim
authors: K
authors: Husain
authors: Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Barbara Ann
authors: BA
authors: Centeno
authors: Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Anthony M
authors: AM
authors: Magliocco
authors: Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Domenico
authors: D
authors: Coppola
authors: Gastrointestinal Surgical Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Mokenge
authors: M
authors: Malafa
mesh_terms: D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D002291:Carcinoma, Papillary / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D057234:Preoperative Period; D011446:Prospective Studies; D011786:Quality Control; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs