MicroRNA-196a and -196b as potential biomarkers for the early detection of familial pancreatic cancer

Emily P. Slater, Konstantin Strauch, Susanne Rospleszcz, Annette Ramaswamy, Irene Esposito, Günter Klöppel, Elvira Matthäi, Kristin Heeger, Volker Fendrich, Peter Langer, Detlef K. Bartsch

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Screening programs are recommended for individuals at risk (IAR) fromfamilies with familial pancreatic cancer (FPC). However, reliable imaging methods or biomarkers for early diagnosis of pancreatic ductal adenocarcinoma (PC) or its precursor lesions are still lacking. The ability of circulating microRNAs (miRNAs) to discriminate multifocal high-grade precursor lesions or PC from normal was examined. The presence of miRNA-21, -155, -196a, -196b and -210 was analyzed in the serumof transgenic KPCmice to test their ability to distinguish mice with different grades of pancreatic intraepithelial neoplasia (mPanIN1-3) or PC from control mice. Serum levels ofmiR-196a and -196b were significantly higher in mice with PanIN2/3 lesions (n = 10) or PC (n = 8) as compared to control mice (n = 10) or mice with PanIN1 lesions (n = 10; P =.01). In humans, miR-196a and -196b were also diagnostic. Patients with PC, sporadic (n = 9) or hereditary (n=10), and IARwithmultifocal PanIN2/3 lesions (n=5) had significantly higher serumlevels than patients with neuroendocrine pancreatic tumors (n = 10) or chronic pancreatitis (n = 10), IAR with PanIN1 or no PanIN lesions (n = 5), and healthy controls (n = 10). The combination of both miR-196a and -196b reached a sensitivity of 1 and specificity of 0.9 (area under the curve = 0.99) to diagnose PC or high-grade PanIN lesions. In addition, preoperative elevated serumlevels ofmiR-196a and -196b in patientswith PC ormultifocal PanIN2/3 lesions dropped to normal after potential curative resection. The combination of miR-196a and -196b may be a promising biomarker test for the screening of IAR for FPC.

Original languageEnglish
Pages (from-to)464-471
Number of pages8
JournalTranslational Oncology
Volume7
Issue number4
DOIs
StatePublished - Aug 2014

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