title: Endoscopically acquired pancreatic cyst fluid microRNA 21 and 221 are associated with invasive cancer.
abstract: OBJECTIVE
  Pancreatic cysts are a group of lesions with heterogeneous malignant potential. Currently, there are no reliable biomarkers to aid in cyst diagnosis and classification. The objective of this study was to identify potential microRNA (miR) biomarkers in endoscopically acquired pancreatic cyst fluid that could be used to distinguish between benign, premalignant, and malignant cysts.
  
  
  METHODS
  A list of candidate miRs was developed using a whole-genome expression array analysis of pancreatic cancer (pancreatic ductal adenocarcinoma) and nonmalignant samples overlapped with existing literature and predicted gene targets. Endoscopically acquired pancreatic cyst fluid samples were obtained from a group of 38 patients who underwent cyst fluid aspiration and surgical resection. Selected miR expression levels in cyst fluid samples were assessed by quantitative real-time-PCR. Additionally, in situ hybridization (ISH) on corresponding cyst tissue samples was performed to identify the source and validate the expression level of fluid miRs.
  
  
  RESULTS
  Of the six miRs that were profiled in the study, two showed differential expression in malignant cysts. miR-221 was expressed at significantly higher levels in malignant cysts compared with benign or premalignant cysts (P=0.05). miR-21 was also expressed at significantly higher levels in malignant cysts (P<0.01). Additionally, the expression of miR-21 was significantly higher in premalignant cysts than benign cysts (P=0.03). The differential expression of miR-21 among cyst categories was confirmed by ISH.
  
  
  CONCLUSIONS
  In this small single-center study, miRs are potential pancreatic cyst fluid diagnostic biomarkers. In particular, miR-21 is identified as a candidate biomarker to distinguish between benign, premalignant, and malignant cysts. Additionally miR-221 may be of use in the identification of more advanced malignant disease.
authors.affiliation: Section of Digestive Diseases, Yale Center for Pancreatic Disease, Yale SOM, New Haven, CT 06510-3221, USA. james.j.farrell@yale.edu
authors.forename: James J
authors.initials: JJ
authors.lastname: Farrell
authors.forename: Paul
authors.initials: P
authors.lastname: Toste
authors.forename: Nanping
authors.initials: N
authors.lastname: Wu
authors.forename: Luyi
authors.initials: L
authors.lastname: Li
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wong
authors.forename: Daniel
authors.initials: D
authors.lastname: Malkhassian
authors.forename: Linh M
authors.initials: LM
authors.lastname: Tran
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wu
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Dawson
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Donahue
mesh_terms: D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology*; D020420:Cyst Fluid / Q000737:chemistry* / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D010181:Pancreatic Cyst / Q000378:metabolism* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs