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Extracellular Vesicle-Based Detection of Pancreatic Cancer
Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tis...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343017/ https://www.ncbi.nlm.nih.gov/pubmed/34368146 http://dx.doi.org/10.3389/fcell.2021.697939 |
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author | Verel-Yilmaz, Yesim Fernández, Juan Pablo Schäfer, Agnes Nevermann, Sheila Cook, Lena Gercke, Norman Helmprobst, Frederik Jaworek, Christian Pogge von Strandmann, Elke Pagenstecher, Axel Bartsch, Detlef K. Bartsch, Jörg W. Slater, Emily P. |
author_facet | Verel-Yilmaz, Yesim Fernández, Juan Pablo Schäfer, Agnes Nevermann, Sheila Cook, Lena Gercke, Norman Helmprobst, Frederik Jaworek, Christian Pogge von Strandmann, Elke Pagenstecher, Axel Bartsch, Detlef K. Bartsch, Jörg W. Slater, Emily P. |
author_sort | Verel-Yilmaz, Yesim |
collection | PubMed |
description | Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC. |
format | Online Article Text |
id | pubmed-8343017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83430172021-08-07 Extracellular Vesicle-Based Detection of Pancreatic Cancer Verel-Yilmaz, Yesim Fernández, Juan Pablo Schäfer, Agnes Nevermann, Sheila Cook, Lena Gercke, Norman Helmprobst, Frederik Jaworek, Christian Pogge von Strandmann, Elke Pagenstecher, Axel Bartsch, Detlef K. Bartsch, Jörg W. Slater, Emily P. Front Cell Dev Biol Cell and Developmental Biology Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC. Frontiers Media S.A. 2021-07-23 /pmc/articles/PMC8343017/ /pubmed/34368146 http://dx.doi.org/10.3389/fcell.2021.697939 Text en Copyright © 2021 Verel-Yilmaz, Fernández, Schäfer, Nevermann, Cook, Gercke, Helmprobst, Jaworek, Pogge von Strandmann, Pagenstecher, Bartsch, Bartsch and Slater. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Verel-Yilmaz, Yesim Fernández, Juan Pablo Schäfer, Agnes Nevermann, Sheila Cook, Lena Gercke, Norman Helmprobst, Frederik Jaworek, Christian Pogge von Strandmann, Elke Pagenstecher, Axel Bartsch, Detlef K. Bartsch, Jörg W. Slater, Emily P. Extracellular Vesicle-Based Detection of Pancreatic Cancer |
title | Extracellular Vesicle-Based Detection of Pancreatic Cancer |
title_full | Extracellular Vesicle-Based Detection of Pancreatic Cancer |
title_fullStr | Extracellular Vesicle-Based Detection of Pancreatic Cancer |
title_full_unstemmed | Extracellular Vesicle-Based Detection of Pancreatic Cancer |
title_short | Extracellular Vesicle-Based Detection of Pancreatic Cancer |
title_sort | extracellular vesicle-based detection of pancreatic cancer |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343017/ https://www.ncbi.nlm.nih.gov/pubmed/34368146 http://dx.doi.org/10.3389/fcell.2021.697939 |
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