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Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and aggressive cancers with a less than 6% five-year survival rate. Circulating microRNAs (miRNAs) are emerging as a useful tool for non-invasive diagnosis and prognosis estimation in the various cancer types, including PDAC. Our stud...

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Autores principales: Gablo, Natalia, Trachtova, Karolina, Prochazka, Vladimir, Hlavsa, Jan, Grolich, Tomas, Kiss, Igor, Srovnal, Josef, Rehulkova, Alona, Lovecek, Martin, Skalicky, Pavel, Berindan-Neagoe, Ioana, Kala, Zdenek, Slaby, Ondrej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464450/
https://www.ncbi.nlm.nih.gov/pubmed/32751582
http://dx.doi.org/10.3390/jcm9082440
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author Gablo, Natalia
Trachtova, Karolina
Prochazka, Vladimir
Hlavsa, Jan
Grolich, Tomas
Kiss, Igor
Srovnal, Josef
Rehulkova, Alona
Lovecek, Martin
Skalicky, Pavel
Berindan-Neagoe, Ioana
Kala, Zdenek
Slaby, Ondrej
author_facet Gablo, Natalia
Trachtova, Karolina
Prochazka, Vladimir
Hlavsa, Jan
Grolich, Tomas
Kiss, Igor
Srovnal, Josef
Rehulkova, Alona
Lovecek, Martin
Skalicky, Pavel
Berindan-Neagoe, Ioana
Kala, Zdenek
Slaby, Ondrej
author_sort Gablo, Natalia
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and aggressive cancers with a less than 6% five-year survival rate. Circulating microRNAs (miRNAs) are emerging as a useful tool for non-invasive diagnosis and prognosis estimation in the various cancer types, including PDAC. Our study aimed to evaluate whether miRNAs in the pre-operative blood plasma specimen have the potential to predict the prognosis of PDAC patients. In total, 112 PDAC patients planned for surgical resection were enrolled in our prospective study. To identify prognostic miRNAs, we used small RNA sequencing in 24 plasma samples of PDAC patients with poor prognosis (overall survival (OS) < 16 months) and 24 plasma samples of PDAC patients with a good prognosis (OS > 20 months). qPCR validation of selected miRNA candidates was performed in the independent cohort of PDAC patients (n = 64). In the discovery phase of the study, we identified 44 miRNAs with significantly different levels in the plasma samples of the group of good and poor prognosis patients. Among these miRNAs, 23 showed lower levels, and 21 showed higher levels in plasma specimens from PDAC patients with poor prognosis. Eleven miRNAs were selected for the validation, but only miR-99a-5p and miR-365a-3p were confirmed to have significantly lower levels and miR-200c-3p higher levels in plasma samples of poor prognosis cases. Using the combination of these 3-miRNA levels, we were able to identify the patients with poor prognosis with sensitivity 85% and specificity 80% (Area Under the Curve = 0.890). Overall, 3-miRNA prognostic score associated with OS was identified in the pre-operative blood plasma samples of PDAC patients undergoing surgical resection. Following further independent validations, the detection of these miRNA may enable identification of PDAC patients who have no survival benefit from the surgical treatment, which is associated with the high morbidity rates.
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spelling pubmed-74644502020-09-04 Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection Gablo, Natalia Trachtova, Karolina Prochazka, Vladimir Hlavsa, Jan Grolich, Tomas Kiss, Igor Srovnal, Josef Rehulkova, Alona Lovecek, Martin Skalicky, Pavel Berindan-Neagoe, Ioana Kala, Zdenek Slaby, Ondrej J Clin Med Article Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and aggressive cancers with a less than 6% five-year survival rate. Circulating microRNAs (miRNAs) are emerging as a useful tool for non-invasive diagnosis and prognosis estimation in the various cancer types, including PDAC. Our study aimed to evaluate whether miRNAs in the pre-operative blood plasma specimen have the potential to predict the prognosis of PDAC patients. In total, 112 PDAC patients planned for surgical resection were enrolled in our prospective study. To identify prognostic miRNAs, we used small RNA sequencing in 24 plasma samples of PDAC patients with poor prognosis (overall survival (OS) < 16 months) and 24 plasma samples of PDAC patients with a good prognosis (OS > 20 months). qPCR validation of selected miRNA candidates was performed in the independent cohort of PDAC patients (n = 64). In the discovery phase of the study, we identified 44 miRNAs with significantly different levels in the plasma samples of the group of good and poor prognosis patients. Among these miRNAs, 23 showed lower levels, and 21 showed higher levels in plasma specimens from PDAC patients with poor prognosis. Eleven miRNAs were selected for the validation, but only miR-99a-5p and miR-365a-3p were confirmed to have significantly lower levels and miR-200c-3p higher levels in plasma samples of poor prognosis cases. Using the combination of these 3-miRNA levels, we were able to identify the patients with poor prognosis with sensitivity 85% and specificity 80% (Area Under the Curve = 0.890). Overall, 3-miRNA prognostic score associated with OS was identified in the pre-operative blood plasma samples of PDAC patients undergoing surgical resection. Following further independent validations, the detection of these miRNA may enable identification of PDAC patients who have no survival benefit from the surgical treatment, which is associated with the high morbidity rates. MDPI 2020-07-30 /pmc/articles/PMC7464450/ /pubmed/32751582 http://dx.doi.org/10.3390/jcm9082440 Text en © 2020 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
Gablo, Natalia
Trachtova, Karolina
Prochazka, Vladimir
Hlavsa, Jan
Grolich, Tomas
Kiss, Igor
Srovnal, Josef
Rehulkova, Alona
Lovecek, Martin
Skalicky, Pavel
Berindan-Neagoe, Ioana
Kala, Zdenek
Slaby, Ondrej
Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection
title Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection
title_full Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection
title_fullStr Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection
title_full_unstemmed Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection
title_short Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection
title_sort identification and validation of circulating micrornas as prognostic biomarkers in pancreatic ductal adenocarcinoma patients undergoing surgical resection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464450/
https://www.ncbi.nlm.nih.gov/pubmed/32751582
http://dx.doi.org/10.3390/jcm9082440
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