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The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer

1
Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, D-35043 Marburg, Germany
2
Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Faculty of Medicine, Ludwig-Maximilians-Universität, Marchioninistr. 15, D-81377 Munich, Germany
3
Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
4
Department of Gastroenterology, Endocrinology and Metabolism, Philipps University Marburg, Baldingerstrasse, D-35043 Marburg, Germany
5
Department of Diagnostic and Interventional Radiology, Philipps University Marburg, Baldingerstrasse, D-35043 Marburg, Germany
6
Department of Hematology, Oncology and Immunology, Philipps University Marburg, Baldingerstrasse, D-35043 Marburg, Germany
7
Center for Tumor and Immune Biology, Philipps University Marburg, Hans-Meerwein-Str. 3, D-35043 Marburg, Germany
8
Department of Pathology, Technical University Munich, Trogerstr. 18, D-81675 Munich, Germany
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2018, 7(10), 295; https://doi.org/10.3390/jcm7100295
Received: 29 August 2018 / Revised: 14 September 2018 / Accepted: 18 September 2018 / Published: 20 September 2018
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Abstract

Individuals at risk (IAR) of familial pancreatic cancer (FPC) are good candidates for screening. Unfortunately, neither reliable imaging modalities nor biomarkers are available to detect high-grade precursor lesions or early cancer. Circulating levels of candidate biomarkers LCN2, TIMP1, Glypican-1, RNU2-1f, and miRNA-196b were analyzed in 218 individuals with sporadic pancreatic ductal adenocarcinoma (PDAC, n = 50), FPC (n = 20), chronic pancreatitis (n = 10), IAR with relevant precursor lesions (n = 11) or non-relevant lesions (n = 5), 20 controls, and IAR with (n = 51) or without (n = 51) lesions on pancreatic imaging. In addition, corresponding duodenal juice samples were analyzed for Glypican-1 (n = 144) enrichment and KRAS mutations (n = 123). The panel miR-196b/LCN2/TIMP1 could distinguish high-grade lesions and stage I PDAC from controls with absolute specificity and sensitivity. In contrast, Glypican-1 enrichment in serum exosomes and duodenal juice was not diagnostic. KRAS mutations in duodenal juice were detected in 9 of 12 patients with PDAC and only 4 of 9 IAR with relevant precursor lesions. IAR with lesions on imaging had elevated miR-196b/LCN2/TIMP1 levels (p = 0.0007) and KRAS mutations in duodenal juice (p = 0.0004) significantly more often than IAR without imaging lesions. The combination miR-196b/LCN2/TIMP1 might be a promising biomarker set for the detection of high-grade PDAC precursor lesions in IAR of FPC families. View Full-Text
Keywords: pancreatic ductal adenocarcinoma; LCN2/NGAL; TIMP1; Glypican-1; miRNA-196b; KRAS mutation pancreatic ductal adenocarcinoma; LCN2/NGAL; TIMP1; Glypican-1; miRNA-196b; KRAS mutation
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Bartsch, D.K.; Gercke, N.; Strauch, K.; Wieboldt, R.; Matthäi, E.; Wagner, V.; Rospleszcz, S.; Schäfer, A.; Franke, F.S.; Mintziras, I.; Bauer, C.; Grote, T.; Figiel, J.; Di Fazio, P.; Burchert, A.; Reinartz, S.; Pogge von Strandmann, E.; Klöppel, G.; Slater, E.P. The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer. J. Clin. Med. 2018, 7, 295.

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