MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer

Evidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but few have compared primary tumor and sentinel lymph node (SLN) metastasis. We correlated the expression of miRNAs with the...

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Main Authors: Daniel Escuin, Laura López-Vilaró, Olga Bell, Josefina Mora, Antonio Moral, José Ignacio Pérez, Cristina Arqueros, Teresa Ramón y Cajal, Enrique Lerma, Agustí Barnadas
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-12-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2020.562114/full
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author Daniel Escuin
Laura López-Vilaró
Laura López-Vilaró
Olga Bell
Josefina Mora
Antonio Moral
Antonio Moral
José Ignacio Pérez
Cristina Arqueros
Teresa Ramón y Cajal
Enrique Lerma
Enrique Lerma
Enrique Lerma
Agustí Barnadas
Agustí Barnadas
Agustí Barnadas
Agustí Barnadas
author_facet Daniel Escuin
Laura López-Vilaró
Laura López-Vilaró
Olga Bell
Josefina Mora
Antonio Moral
Antonio Moral
José Ignacio Pérez
Cristina Arqueros
Teresa Ramón y Cajal
Enrique Lerma
Enrique Lerma
Enrique Lerma
Agustí Barnadas
Agustí Barnadas
Agustí Barnadas
Agustí Barnadas
author_sort Daniel Escuin
collection DOAJ
description Evidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but few have compared primary tumor and sentinel lymph node (SLN) metastasis. We correlated the expression of miRNAs with the SLN status and the outcome of axillary lymph node dissection (ALND) in 60 patients with early breast cancer. We profiled the expression of miRNAs in paired breast tumor samples and SLNs using the NextSeq500 Illumina platform and key findings were validated by qPCR. MultiMiR Bioconductor and Reactome pathways analysis were performed to identify target genes and signaling pathways affected by altered expressed miRNAs. Our results show that nine miRNAs were differentially expressed in tumor tissues (q ≤ 0.05). In tumor samples, a 13.5-fold up-regulation of miR-7641-2 (q < 0.001) and a 2.9-fold down-regulation of miR-1291 (q < 0.001) were associated with tumors with positive SLNs. However, only down-regulation of miR-1291 (q = 0.048) remained significant in paired SLNs samples. Interestingly, a 10.5 up-regulation of miR-1291 in SLNs samples was associated with additional axillary lymph node involvement (q < 0.001). The enrichment analyses showed that canonical and non-canonical WNT pathways and negative regulation of various receptor tyrosine kinases signaling pathways were targets of miR-1291 and supports the role of miR-1291 as a tumor suppressor gene (TSG). Further studies are warranted to investigate the use of miR-1291 as a surrogate biomarker of SLN node metastasis in patients with early-stage breast cancer.
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spelling doaj.art-7b2626ae3d964deaa6751f0bd6488ccd2022-12-21T23:19:00ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-12-011110.3389/fgene.2020.562114562114MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast CancerDaniel Escuin0Laura López-Vilaró1Laura López-Vilaró2Olga Bell3Josefina Mora4Antonio Moral5Antonio Moral6José Ignacio Pérez7Cristina Arqueros8Teresa Ramón y Cajal9Enrique Lerma10Enrique Lerma11Enrique Lerma12Agustí Barnadas13Agustí Barnadas14Agustí Barnadas15Agustí Barnadas16Institut d’Investigació Biomèdica Sant Pau, Barcelona, SpainInstitut d’Investigació Biomèdica Sant Pau, Barcelona, SpainHospital de la Santa Creu i Sant Pau, Barcelona, SpainInstitut d’Investigació Biomèdica Sant Pau, Barcelona, SpainHospital de la Santa Creu i Sant Pau, Barcelona, SpainHospital de la Santa Creu i Sant Pau, Barcelona, SpainDepartment of Medicine, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), SpainHospital de la Santa Creu i Sant Pau, Barcelona, SpainHospital de la Santa Creu i Sant Pau, Barcelona, SpainHospital de la Santa Creu i Sant Pau, Barcelona, SpainInstitut d’Investigació Biomèdica Sant Pau, Barcelona, SpainHospital de la Santa Creu i Sant Pau, Barcelona, SpainDepartment of Medicine, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), SpainInstitut d’Investigació Biomèdica Sant Pau, Barcelona, SpainHospital de la Santa Creu i Sant Pau, Barcelona, SpainDepartment of Medicine, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), SpainCentro de Investigación Biomédica en Red Cáncer, Madrid, SpainEvidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but few have compared primary tumor and sentinel lymph node (SLN) metastasis. We correlated the expression of miRNAs with the SLN status and the outcome of axillary lymph node dissection (ALND) in 60 patients with early breast cancer. We profiled the expression of miRNAs in paired breast tumor samples and SLNs using the NextSeq500 Illumina platform and key findings were validated by qPCR. MultiMiR Bioconductor and Reactome pathways analysis were performed to identify target genes and signaling pathways affected by altered expressed miRNAs. Our results show that nine miRNAs were differentially expressed in tumor tissues (q ≤ 0.05). In tumor samples, a 13.5-fold up-regulation of miR-7641-2 (q < 0.001) and a 2.9-fold down-regulation of miR-1291 (q < 0.001) were associated with tumors with positive SLNs. However, only down-regulation of miR-1291 (q = 0.048) remained significant in paired SLNs samples. Interestingly, a 10.5 up-regulation of miR-1291 in SLNs samples was associated with additional axillary lymph node involvement (q < 0.001). The enrichment analyses showed that canonical and non-canonical WNT pathways and negative regulation of various receptor tyrosine kinases signaling pathways were targets of miR-1291 and supports the role of miR-1291 as a tumor suppressor gene (TSG). Further studies are warranted to investigate the use of miR-1291 as a surrogate biomarker of SLN node metastasis in patients with early-stage breast cancer.https://www.frontiersin.org/articles/10.3389/fgene.2020.562114/fullaxillary lymph node dissectionbreast cancersentinel lymph nodemetastasismicroRNAs
spellingShingle Daniel Escuin
Laura López-Vilaró
Laura López-Vilaró
Olga Bell
Josefina Mora
Antonio Moral
Antonio Moral
José Ignacio Pérez
Cristina Arqueros
Teresa Ramón y Cajal
Enrique Lerma
Enrique Lerma
Enrique Lerma
Agustí Barnadas
Agustí Barnadas
Agustí Barnadas
Agustí Barnadas
MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer
Frontiers in Genetics
axillary lymph node dissection
breast cancer
sentinel lymph node
metastasis
microRNAs
title MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer
title_full MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer
title_fullStr MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer
title_full_unstemmed MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer
title_short MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer
title_sort microrna 1291 is associated with locoregional metastases in patients with early stage breast cancer
topic axillary lymph node dissection
breast cancer
sentinel lymph node
metastasis
microRNAs
url https://www.frontiersin.org/articles/10.3389/fgene.2020.562114/full
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