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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

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,...

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Autores principales: Bartsch, Detlef K., Gercke, Norman, Strauch, Konstantin, Wieboldt, Ronja, Matthäi, Elvira, Wagner, Vinona, Rospleszcz, Susanne, Schäfer, Agnes, Franke, Frederike S., Mintziras, Ioannis, Bauer, Christian, Grote, Tobias, Figiel, Jens, Di Fazio, Pietro, Burchert, Andreas, Reinartz, Silke, Pogge von Strandmann, Elke, Klöppel, Günter, Slater, Emily P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210952/
https://www.ncbi.nlm.nih.gov/pubmed/30241369
http://dx.doi.org/10.3390/jcm7100295
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author Bartsch, Detlef K.
Gercke, Norman
Strauch, Konstantin
Wieboldt, Ronja
Matthäi, Elvira
Wagner, Vinona
Rospleszcz, Susanne
Schäfer, Agnes
Franke, Frederike S.
Mintziras, Ioannis
Bauer, Christian
Grote, Tobias
Figiel, Jens
Di Fazio, Pietro
Burchert, Andreas
Reinartz, Silke
Pogge von Strandmann, Elke
Klöppel, Günter
Slater, Emily P.
author_facet Bartsch, Detlef K.
Gercke, Norman
Strauch, Konstantin
Wieboldt, Ronja
Matthäi, Elvira
Wagner, Vinona
Rospleszcz, Susanne
Schäfer, Agnes
Franke, Frederike S.
Mintziras, Ioannis
Bauer, Christian
Grote, Tobias
Figiel, Jens
Di Fazio, Pietro
Burchert, Andreas
Reinartz, Silke
Pogge von Strandmann, Elke
Klöppel, Günter
Slater, Emily P.
author_sort Bartsch, Detlef K.
collection PubMed
description 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.
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spelling pubmed-62109522018-11-02 The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer Bartsch, Detlef K. Gercke, Norman Strauch, Konstantin Wieboldt, Ronja Matthäi, Elvira Wagner, Vinona Rospleszcz, Susanne Schäfer, Agnes Franke, Frederike S. Mintziras, Ioannis Bauer, Christian Grote, Tobias Figiel, Jens Di Fazio, Pietro Burchert, Andreas Reinartz, Silke Pogge von Strandmann, Elke Klöppel, Günter Slater, Emily P. J Clin Med Article 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. MDPI 2018-09-20 /pmc/articles/PMC6210952/ /pubmed/30241369 http://dx.doi.org/10.3390/jcm7100295 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bartsch, Detlef K.
Gercke, Norman
Strauch, Konstantin
Wieboldt, Ronja
Matthäi, Elvira
Wagner, Vinona
Rospleszcz, Susanne
Schäfer, Agnes
Franke, Frederike S.
Mintziras, Ioannis
Bauer, Christian
Grote, Tobias
Figiel, Jens
Di Fazio, Pietro
Burchert, Andreas
Reinartz, Silke
Pogge von Strandmann, Elke
Klöppel, Günter
Slater, Emily 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
title The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer
title_full The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer
title_fullStr The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer
title_full_unstemmed The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer
title_short The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer
title_sort combination of mirna-196b, lcn2, and timp1 is a potential set of circulating biomarkers for screening individuals at risk for familial pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210952/
https://www.ncbi.nlm.nih.gov/pubmed/30241369
http://dx.doi.org/10.3390/jcm7100295
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