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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,...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6210952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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