title: MicroRNA expression signatures in intraductal papillary mucinous neoplasm of the pancreas.
abstract: BACKGROUND
  Intraductal papillary mucinous neoplasms (IPMN) represent a spectrum of tumors that range from low-grade (LG) dysplastic tumors to invasive cancer. Identification of IPMN at high risk for malignant transformation is important for the prevention and early treatment of pancreatic cancer. The roles of microRNA expression in the development of IPMN have not been extensively evaluated.
  
  
  METHODS
  Expression patterns of 846 human microRNAs (miRNAs) was analyzed using microRNA microarray in 55 tissues, including LG IPMN (n = 10), moderate-grade (MG) IPMN (n = 5), high-grade (HG) IPMN (n = 5), invasive cancer with IPMN (IPMC; n = 10), pancreatic ductal adenocarcinoma without IPMN (PDA; n = 5), LG IPMN extracted from specimens that contain IPMC (LG_Ca; n = 10), and normal pancreatic tissues (n = 10).
  
  
  RESULTS
  Fourteen miRNAs were differentially expressed in all IPMN tissues compared with normal pancreatic tissue. Expression level of 3 miRNAs was proportional to dysplasia level. Hierarchical clustering demonstrated grouping of 2 IPMN subgroups: LG and MG IPMN verses HG IPMN and IPMC. Expression of 15 miRNAs was significantly different between these groups. LG_Ca tissues clustered with the HG IPMC group, and 12 miRNAs were differentially expressed in LG_Ca, HG lesions, and IPMC compared with LG lesions. The expression patterns of selected miRNAs were validated using quantitative reverse-transcription real-time polymerase chain reaction. Hierarchical clustering demonstrated microRNA expression profile in IPMC was significantly different from PDA, suggesting that different pathways are involved in these cancer types.
  
  
  CONCLUSIONS
  This study demonstrates that miRNAs are involved in the development and progression of IPMN. We identified potential targets for diagnosis, prognostication, and treatment of IPMN.
authors.affiliation: Department of Surgery and Nicolas and Elizabeth Slezak Cathedra in Experimental Surgery, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. nir_lubezky@hotmail.com
authors.forename: Nir
authors.initials: N
authors.lastname: Lubezky
authors.forename: Shelly
authors.initials: S
authors.lastname: Loewenstein
authors.forename: Menahem
authors.initials: M
authors.lastname: Ben-Haim
authors.forename: Eli
authors.initials: E
authors.lastname: Brazowski
authors.forename: Sylvia
authors.initials: S
authors.lastname: Marmor
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.forename: Varda
authors.initials: V
authors.lastname: Oron-Karni
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Klausner
authors.forename: Guy
authors.initials: G
authors.lastname: Lahat
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs