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Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers

BACKGROUND: The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers. METHODS: Expression of 46 selected microRNAs was studied in formalin-fixed paraffin-em...

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Autores principales: Calatayud, Dan, Dehlendorff, Christian, Boisen, Mogens K., Hasselby, Jane Preuss, Schultz, Nicolai Aagaard, Werner, Jens, Immervoll, Heike, Molven, Anders, Hansen, Carsten Palnæs, Johansen, Julia S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320745/
https://www.ncbi.nlm.nih.gov/pubmed/28239461
http://dx.doi.org/10.1186/s40364-017-0087-6
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author Calatayud, Dan
Dehlendorff, Christian
Boisen, Mogens K.
Hasselby, Jane Preuss
Schultz, Nicolai Aagaard
Werner, Jens
Immervoll, Heike
Molven, Anders
Hansen, Carsten Palnæs
Johansen, Julia S.
author_facet Calatayud, Dan
Dehlendorff, Christian
Boisen, Mogens K.
Hasselby, Jane Preuss
Schultz, Nicolai Aagaard
Werner, Jens
Immervoll, Heike
Molven, Anders
Hansen, Carsten Palnæs
Johansen, Julia S.
author_sort Calatayud, Dan
collection PubMed
description BACKGROUND: The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers. METHODS: Expression of 46 selected microRNAs was studied in formalin-fixed paraffin-embedded tissue from patients with resected pancreatic ductal adenocarcinoma (n = 165), ampullary cancer (n=59), duodenal cancer (n = 6), distal common bile duct cancer (n = 21), and gastric cancer (n = 20); chronic pancreatitis (n = 39); and normal pancreas (n = 35). The microRNAs were analyzed by PCR using the Fluidigm platform. RESULTS: Twenty-two microRNAs were significantly differently expressed in patients with pancreatic cancer when compared to healthy controls and chronic pancreatitis patients; 17 miRNAs were upregulated (miR-21-5p, −23a-3p, −31-5p, −34c-5p, −93-3p, −135b-3p, −155-5p, −186-5p, −196b-5p, −203, −205-5p, −210, −222-3p, −451, −492, −614, and miR-622) and 5 were downregulated (miR-122-5p, −130b-3p, −216b, −217, and miR-375). MicroRNAs were grouped into diagnostic indices of varying complexity. Ten microRNAs associated with prognosis were identified (let-7 g, miR-29a-5p, −34a-5p, −125a-3p, −146a-5p, −187, −205-5p, −212-3p, −222-5p, and miR-450b-5p). Prognostic indices based on differences in expression of 2 different microRNAs were constructed for pancreatic and ampullary cancer combined and separately (30, 5, and 21 indices). CONCLUSION: The study confirms that pancreatic cancer tissue has a microRNA expression profile that is different from that of other periampullary cancers, chronic pancreatitis, and normal pancreas. We identified prognostic microRNAs and microRNA indices that were associated with shorter overall survival in patients with radically resected pancreatic cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40364-017-0087-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-53207452017-02-24 Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers Calatayud, Dan Dehlendorff, Christian Boisen, Mogens K. Hasselby, Jane Preuss Schultz, Nicolai Aagaard Werner, Jens Immervoll, Heike Molven, Anders Hansen, Carsten Palnæs Johansen, Julia S. Biomark Res Research BACKGROUND: The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers. METHODS: Expression of 46 selected microRNAs was studied in formalin-fixed paraffin-embedded tissue from patients with resected pancreatic ductal adenocarcinoma (n = 165), ampullary cancer (n=59), duodenal cancer (n = 6), distal common bile duct cancer (n = 21), and gastric cancer (n = 20); chronic pancreatitis (n = 39); and normal pancreas (n = 35). The microRNAs were analyzed by PCR using the Fluidigm platform. RESULTS: Twenty-two microRNAs were significantly differently expressed in patients with pancreatic cancer when compared to healthy controls and chronic pancreatitis patients; 17 miRNAs were upregulated (miR-21-5p, −23a-3p, −31-5p, −34c-5p, −93-3p, −135b-3p, −155-5p, −186-5p, −196b-5p, −203, −205-5p, −210, −222-3p, −451, −492, −614, and miR-622) and 5 were downregulated (miR-122-5p, −130b-3p, −216b, −217, and miR-375). MicroRNAs were grouped into diagnostic indices of varying complexity. Ten microRNAs associated with prognosis were identified (let-7 g, miR-29a-5p, −34a-5p, −125a-3p, −146a-5p, −187, −205-5p, −212-3p, −222-5p, and miR-450b-5p). Prognostic indices based on differences in expression of 2 different microRNAs were constructed for pancreatic and ampullary cancer combined and separately (30, 5, and 21 indices). CONCLUSION: The study confirms that pancreatic cancer tissue has a microRNA expression profile that is different from that of other periampullary cancers, chronic pancreatitis, and normal pancreas. We identified prognostic microRNAs and microRNA indices that were associated with shorter overall survival in patients with radically resected pancreatic cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40364-017-0087-6) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-21 /pmc/articles/PMC5320745/ /pubmed/28239461 http://dx.doi.org/10.1186/s40364-017-0087-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Calatayud, Dan
Dehlendorff, Christian
Boisen, Mogens K.
Hasselby, Jane Preuss
Schultz, Nicolai Aagaard
Werner, Jens
Immervoll, Heike
Molven, Anders
Hansen, Carsten Palnæs
Johansen, Julia S.
Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers
title Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers
title_full Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers
title_fullStr Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers
title_full_unstemmed Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers
title_short Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers
title_sort tissue microrna profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320745/
https://www.ncbi.nlm.nih.gov/pubmed/28239461
http://dx.doi.org/10.1186/s40364-017-0087-6
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