The protein and miRNA profile of plasma extracellular vesicles (EVs) can distinguish feline mammary adenocarcinoma patients from healthy feline controls

Abstract Feline mammary adenocarcinomas (FMA) are aggressive tumours with metastatic capability and limited treatment options. This study aims to investigate whether miRNAs associated with FMA tumours are secreted in extracellular vesicles (EVs) and whether they can potentially be used as a cancer b...

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Main Authors: Jane Howard, John Browne, Stephanie Bollard, Susan Peters, Ciara Sweeney, Kieran Wynne, Shirley Potter, Amanda McCann, Pamela Kelly
Format: Article
Language:English
Published: Nature Portfolio 2023-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-36110-7
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author Jane Howard
John Browne
Stephanie Bollard
Susan Peters
Ciara Sweeney
Kieran Wynne
Shirley Potter
Amanda McCann
Pamela Kelly
author_facet Jane Howard
John Browne
Stephanie Bollard
Susan Peters
Ciara Sweeney
Kieran Wynne
Shirley Potter
Amanda McCann
Pamela Kelly
author_sort Jane Howard
collection DOAJ
description Abstract Feline mammary adenocarcinomas (FMA) are aggressive tumours with metastatic capability and limited treatment options. This study aims to investigate whether miRNAs associated with FMA tumours are secreted in extracellular vesicles (EVs) and whether they can potentially be used as a cancer biomarker in EVs from feline plasma. Tumours and matched tumour free margins from 10 felines with FMA were selected. Following a detailed literature search, RT-qPCR analyses of 90 miRNAs identified 8 miRNAs of interest for further investigation. Tumour tissue, margins and plasma were subsequently collected from a further 10 felines with FMA. EVs were isolated from the plasma. RT-qPCR expression analyses of the 8 miRNAs of interest were carried out in tumour tissue, margins, FMA EVs and control EVs. Additionally, proteomic analysis of both control and FMA plasma derived EVs was undertaken. RT-qPCR revealed significantly increased miR-20a and miR-15b in tumours compared to margins. A significant decrease in miR-15b and miR-20a was detected in EVs from FMAs compared to healthy feline EVs. The proteomic content of EVs distinguished FMAs from controls, with the protein targets of miR-20a and miR-15b also displaying lower levels in the EVs from patients with FMA. This study has demonstrated that miRNAs are readily detectable in both the tissue and plasma derived EVs from patients with FMA. These miRNAs and their protein targets are a detectable panel of markers in circulating plasma EVs that may inform future diagnostic tests for FMA in a non-invasive manner. Moreover, the clinical relevance of miR-20a and miR-15b warrants further investigation.
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spelling doaj.art-916206565bf943b784464f1efae0c6822023-06-11T11:10:41ZengNature PortfolioScientific Reports2045-23222023-06-0113111510.1038/s41598-023-36110-7The protein and miRNA profile of plasma extracellular vesicles (EVs) can distinguish feline mammary adenocarcinoma patients from healthy feline controlsJane Howard0John Browne1Stephanie Bollard2Susan Peters3Ciara Sweeney4Kieran Wynne5Shirley Potter6Amanda McCann7Pamela Kelly8UCD School of Medicine, College of Health, and Agricultural Sciences (CHAS), University College DublinUCD School of Agriculture and Food Science, University College DublinUCD School of Medicine, College of Health, and Agricultural Sciences (CHAS), University College DublinCollege of Health and Agricultural Sciences, UCD School of Veterinary Medicine, University College DublinCollege of Health and Agricultural Sciences, UCD School of Veterinary Medicine, University College DublinSystems Biology Ireland, University College DublinUCD School of Medicine, College of Health, and Agricultural Sciences (CHAS), University College DublinUCD School of Medicine, College of Health, and Agricultural Sciences (CHAS), University College DublinCollege of Health and Agricultural Sciences, UCD School of Veterinary Medicine, University College DublinAbstract Feline mammary adenocarcinomas (FMA) are aggressive tumours with metastatic capability and limited treatment options. This study aims to investigate whether miRNAs associated with FMA tumours are secreted in extracellular vesicles (EVs) and whether they can potentially be used as a cancer biomarker in EVs from feline plasma. Tumours and matched tumour free margins from 10 felines with FMA were selected. Following a detailed literature search, RT-qPCR analyses of 90 miRNAs identified 8 miRNAs of interest for further investigation. Tumour tissue, margins and plasma were subsequently collected from a further 10 felines with FMA. EVs were isolated from the plasma. RT-qPCR expression analyses of the 8 miRNAs of interest were carried out in tumour tissue, margins, FMA EVs and control EVs. Additionally, proteomic analysis of both control and FMA plasma derived EVs was undertaken. RT-qPCR revealed significantly increased miR-20a and miR-15b in tumours compared to margins. A significant decrease in miR-15b and miR-20a was detected in EVs from FMAs compared to healthy feline EVs. The proteomic content of EVs distinguished FMAs from controls, with the protein targets of miR-20a and miR-15b also displaying lower levels in the EVs from patients with FMA. This study has demonstrated that miRNAs are readily detectable in both the tissue and plasma derived EVs from patients with FMA. These miRNAs and their protein targets are a detectable panel of markers in circulating plasma EVs that may inform future diagnostic tests for FMA in a non-invasive manner. Moreover, the clinical relevance of miR-20a and miR-15b warrants further investigation.https://doi.org/10.1038/s41598-023-36110-7
spellingShingle Jane Howard
John Browne
Stephanie Bollard
Susan Peters
Ciara Sweeney
Kieran Wynne
Shirley Potter
Amanda McCann
Pamela Kelly
The protein and miRNA profile of plasma extracellular vesicles (EVs) can distinguish feline mammary adenocarcinoma patients from healthy feline controls
Scientific Reports
title The protein and miRNA profile of plasma extracellular vesicles (EVs) can distinguish feline mammary adenocarcinoma patients from healthy feline controls
title_full The protein and miRNA profile of plasma extracellular vesicles (EVs) can distinguish feline mammary adenocarcinoma patients from healthy feline controls
title_fullStr The protein and miRNA profile of plasma extracellular vesicles (EVs) can distinguish feline mammary adenocarcinoma patients from healthy feline controls
title_full_unstemmed The protein and miRNA profile of plasma extracellular vesicles (EVs) can distinguish feline mammary adenocarcinoma patients from healthy feline controls
title_short The protein and miRNA profile of plasma extracellular vesicles (EVs) can distinguish feline mammary adenocarcinoma patients from healthy feline controls
title_sort protein and mirna profile of plasma extracellular vesicles evs can distinguish feline mammary adenocarcinoma patients from healthy feline controls
url https://doi.org/10.1038/s41598-023-36110-7
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