title: Cell-free plasma microRNA in pancreatic ductal adenocarcinoma and disease controls.
abstract: OBJECTIVE
  There are no tumor-specific biochemical markers for pancreatic ductal adenocarcinoma (PDAC). Tissue-specific gene expression including microRNA (miRNA) profiling, however, identifies specific PDAC signatures. This study evaluates associations between circulating, cell-free plasma-miRNA profiles and PDAC in a disease and disease-control cohort.
  
  
  METHODS
  We performed a microarray profiling of 847 different mature miRNAs from plasma in an exploratory cohort of 20 patients with PDAC or other pancreatic diseases, profiling of 45 miRNAs in plasma samples from PDAC (n = 48) and disease controls (n = 47), and evaluation of associations of data with diagnosis, survival, and CA-19-9.
  
  
  RESULTS
  We find 7 significantly deregulated miRNAs in PDAC using univariate statistics. At a false-discovery rate of 5%, miRNA-375 remained significantly elevated in PDAC. MicroRNA-375 did not improve diagnosis of PDAC in this cohort (70% accuracy) and did not correlate with survival. However, 3 controls (other gastrointestinal cancers) with increased CA-19-9 did not show increased miRNA-375.
  
  
  CONCLUSIONS
  In the plasma-miRNA population, we find miRNA-375, which is selectively expressed in the endocrine pancreas under normal conditions, increased in PDAC cases compared with patients with other pancreatic or gastrointestinal diseases. The miRNA-375 does not outperform CA-19-9 diagnostically in the present cohort. However, it shows promising specificity and should be examined in larger prospective studies.
authors.affiliation: From the *Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen; †Department of Medical Gastroenterology, Odense University Hospital, Odense; and ‡Medical Prognosis Institute, Hørsholm, Denmark.
authors.forename: Anting Liu
authors.initials: AL
authors.lastname: Carlsen
authors.forename: Maiken Thyregod
authors.initials: MT
authors.lastname: Joergensen
authors.forename: Steen
authors.initials: S
authors.lastname: Knudsen
authors.forename: Ove B Schaffalitzky
authors.initials: OB
authors.lastname: de Muckadell
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D018395:CA-19-9 Antigen / Q000097:blood; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D002474:Cell-Free System; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm