title: The potential diagnostic value of serum microRNA signature in patients with pancreatic cancer.
abstract: Biomarkers for early diagnosis of patients with pancreatic cancer (PC) are needed. Our aim was to identify panels of miRNAs in serum in combination with CA 19-9 for use in the diagnosis of PC. Four hundred seventeen patients with PC were included prospectively from Denmark (n = 306) and Germany (n = 111). Controls included 59 patients with chronic pancreatitis (CP) and 248 healthy subjects (HS). MiRNAs were analyzed in pretreatment serum samples from 3 cohorts: discovery cohort (754 human miRNAs, TaqMan(®) Human MicroRNA assay, Applied Biosystem; PC n = 133, controls n = 72); training cohort (34 miRNAs, real-time qPCR using the Fluidigm BioMark™ System; PC n = 198, controls n = 184); validation cohort (13 miRNAs, real-time qPCR using the Fluidigm BioMark™ System; PC n = 86, controls n = 51). We found that 34 miRNAs in serum from PC patients in the discovery cohort were expressed differently than in controls. These miRNAs were tested in the training cohort, and four diagnostic panels were constructed that included 5 or 12 miRNAs (miR-16, -18a, -20a, -24, -25, -27a, -29c, -30a.5p, -191, -323.3p, -345 and -483.5p). Diagnostic accuracy of detecting PC in the training cohort was AUC (Index I 0.85; II 0.87; III 0.85; IV 0.95; CA 19-9 0.93); specificity (I 0.71; II 0.76; III 0.66; IV 0.90 (fixed sensitivity at 0.85); CA 19-9 0.93). Combining serum CA 19-9 and Index II best discriminated Stages I and II PC from HS [AUC 0.93 (0.90-0.96), sensitivity 0.77 (0.69-0.84), specificity 0.94 (0.90-0.96) and accuracy 0.88 (0.84-0.91)]. In conclusion, we identified four diagnostic panels based on 5 or 12 miRNAs in serum that could distinguish patients with PC from HS and CP.
authors.affiliation: Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark. julia.johansen@post3.tele.dk.|Department of Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark. julia.johansen@post3.tele.dk.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.affiliation: Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Dan
authors.initials: D
authors.lastname: Calatayud
authors.affiliation: Danish Cancer Society Research Center, Danish Cancer Society, Denmark.
authors.forename: Vanna
authors.initials: V
authors.lastname: Albieri
authors.affiliation: Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Nicolai A
authors.initials: NA
authors.lastname: Schultz
authors.affiliation: Danish Cancer Society Research Center, Danish Cancer Society, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Dehlendorff
authors.affiliation: Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
authors.affiliation: Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.
authors.forename: Benny V
authors.initials: BV
authors.lastname: Jensen
authors.affiliation: Odense University Hospital, Germany.
authors.forename: Per
authors.initials: P
authors.lastname: Pfeiffer
authors.affiliation: Department of Oncology, Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
authors.affiliation: Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Germany.
authors.forename: Nathalia
authors.initials: N
authors.lastname: Giese
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, Denmark.
authors.forename: Kaspar R
authors.initials: KR
authors.lastname: Nielsen
authors.affiliation: Department of Oncology, Hillerød Hospital, Denmark.
authors.forename: Svend E
authors.initials: SE
authors.lastname: Nielsen
authors.affiliation: Department of Oncology, Aalborg University Hospital, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Yilmaz
authors.affiliation: Department of Oncology, Naestved Hospital, Denmark.
authors.forename: Niels H
authors.initials: NH
authors.lastname: Holländer
authors.affiliation: Danish Cancer Society Research Center, Danish Cancer Society, Denmark.
authors.forename: Klaus K
authors.initials: KK
authors.lastname: Andersen
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D006801:Humans; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics*; D050500:Pancreatitis, Chronic / Q000097:blood / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs
keywords: early diagnosis; pancreatic cancer; serum miRNA