Cargando…

A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer

Breast cancers of the luminal B subtype are frequent tumors with high proliferation and poor prognosis. Epigenetic alterations have been found in breast tumors and in biological fluids. We aimed to profile the cell-free DNA (cfDNA) methylome of metastatic luminal B breast cancer (LBBC) patients usin...

Descripción completa

Detalles Bibliográficos
Autores principales: Rodriguez-Casanova, Aitor, Costa-Fraga, Nicolas, Castro-Carballeira, Clara, González-Conde, Miriam, Abuin, Carmen, Bao-Caamano, Aida, García-Caballero, Tomás, Brozos-Vazquez, Elena, Rodriguez-López, Carmela, Cebey, Victor, Palacios, Patricia, Cueva, Juan F., López-López, Rafael, Costa, Clotilde, Díaz-Lagares, Angel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9641197/
https://www.ncbi.nlm.nih.gov/pubmed/36393855
http://dx.doi.org/10.3389/fcell.2022.1016955
_version_ 1784826043971928064
author Rodriguez-Casanova, Aitor
Costa-Fraga, Nicolas
Castro-Carballeira, Clara
González-Conde, Miriam
Abuin, Carmen
Bao-Caamano, Aida
García-Caballero, Tomás
Brozos-Vazquez, Elena
Rodriguez-López, Carmela
Cebey, Victor
Palacios, Patricia
Cueva, Juan F.
López-López, Rafael
Costa, Clotilde
Díaz-Lagares, Angel
author_facet Rodriguez-Casanova, Aitor
Costa-Fraga, Nicolas
Castro-Carballeira, Clara
González-Conde, Miriam
Abuin, Carmen
Bao-Caamano, Aida
García-Caballero, Tomás
Brozos-Vazquez, Elena
Rodriguez-López, Carmela
Cebey, Victor
Palacios, Patricia
Cueva, Juan F.
López-López, Rafael
Costa, Clotilde
Díaz-Lagares, Angel
author_sort Rodriguez-Casanova, Aitor
collection PubMed
description Breast cancers of the luminal B subtype are frequent tumors with high proliferation and poor prognosis. Epigenetic alterations have been found in breast tumors and in biological fluids. We aimed to profile the cell-free DNA (cfDNA) methylome of metastatic luminal B breast cancer (LBBC) patients using an epigenomic approach to discover potential noninvasive biomarkers. Plasma cfDNA was analyzed using the Infinium MethylationEpic array in a cohort of 14 women, including metastatic LBBC patients and nontumor controls. The methylation levels of cfDNA and tissue samples were validated with droplet digital PCR. The methylation and gene expression data of 582 primary luminal breast tumors and 79 nontumor tissues were obtained from The Cancer Genome Atlas (TCGA). We found an episignature of 1,467 differentially methylated CpGs that clearly identified patients with LBBC. Among the genes identified, the promoter hypermethylation of WNT1 was validated in cfDNA, showing an area under the ROC curve (AUC) of 0.86 for the noninvasive detection of metastatic LBBC. Both paired cfDNA and primary/metastatic breast tumor samples showed hypermethylation of WNT1. TCGA analysis revealed significant WNT1 hypermethylation in the primary tumors of luminal breast cancer patients, with a negative association between WNT1 methylation and gene expression. In this proof-of-principle study, we discovered an episignature associated with metastatic LBBC using a genome-wide cfDNA methylation approach. We also identified the promoter hypermethylation of WNT1 in cfDNA as a potential noninvasive biomarker for luminal breast cancer. Our results support the use of EPIC arrays to identify new epigenetic noninvasive biomarkers in breast cancer.
format Online
Article
Text
id pubmed-9641197
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96411972022-11-15 A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer Rodriguez-Casanova, Aitor Costa-Fraga, Nicolas Castro-Carballeira, Clara González-Conde, Miriam Abuin, Carmen Bao-Caamano, Aida García-Caballero, Tomás Brozos-Vazquez, Elena Rodriguez-López, Carmela Cebey, Victor Palacios, Patricia Cueva, Juan F. López-López, Rafael Costa, Clotilde Díaz-Lagares, Angel Front Cell Dev Biol Cell and Developmental Biology Breast cancers of the luminal B subtype are frequent tumors with high proliferation and poor prognosis. Epigenetic alterations have been found in breast tumors and in biological fluids. We aimed to profile the cell-free DNA (cfDNA) methylome of metastatic luminal B breast cancer (LBBC) patients using an epigenomic approach to discover potential noninvasive biomarkers. Plasma cfDNA was analyzed using the Infinium MethylationEpic array in a cohort of 14 women, including metastatic LBBC patients and nontumor controls. The methylation levels of cfDNA and tissue samples were validated with droplet digital PCR. The methylation and gene expression data of 582 primary luminal breast tumors and 79 nontumor tissues were obtained from The Cancer Genome Atlas (TCGA). We found an episignature of 1,467 differentially methylated CpGs that clearly identified patients with LBBC. Among the genes identified, the promoter hypermethylation of WNT1 was validated in cfDNA, showing an area under the ROC curve (AUC) of 0.86 for the noninvasive detection of metastatic LBBC. Both paired cfDNA and primary/metastatic breast tumor samples showed hypermethylation of WNT1. TCGA analysis revealed significant WNT1 hypermethylation in the primary tumors of luminal breast cancer patients, with a negative association between WNT1 methylation and gene expression. In this proof-of-principle study, we discovered an episignature associated with metastatic LBBC using a genome-wide cfDNA methylation approach. We also identified the promoter hypermethylation of WNT1 in cfDNA as a potential noninvasive biomarker for luminal breast cancer. Our results support the use of EPIC arrays to identify new epigenetic noninvasive biomarkers in breast cancer. Frontiers Media S.A. 2022-10-25 /pmc/articles/PMC9641197/ /pubmed/36393855 http://dx.doi.org/10.3389/fcell.2022.1016955 Text en Copyright © 2022 Rodriguez-Casanova, Costa-Fraga, Castro-Carballeira, González-Conde, Abuin, Bao-Caamano, García-Caballero, Brozos-Vazquez, Rodriguez-López, Cebey, Palacios, Cueva, López-López, Costa and Díaz-Lagares. 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
Rodriguez-Casanova, Aitor
Costa-Fraga, Nicolas
Castro-Carballeira, Clara
González-Conde, Miriam
Abuin, Carmen
Bao-Caamano, Aida
García-Caballero, Tomás
Brozos-Vazquez, Elena
Rodriguez-López, Carmela
Cebey, Victor
Palacios, Patricia
Cueva, Juan F.
López-López, Rafael
Costa, Clotilde
Díaz-Lagares, Angel
A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer
title A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer
title_full A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer
title_fullStr A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer
title_full_unstemmed A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer
title_short A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer
title_sort genome-wide cell-free dna methylation analysis identifies an episignature associated with metastatic luminal b breast cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9641197/
https://www.ncbi.nlm.nih.gov/pubmed/36393855
http://dx.doi.org/10.3389/fcell.2022.1016955
work_keys_str_mv AT rodriguezcasanovaaitor agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT costafraganicolas agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT castrocarballeiraclara agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT gonzalezcondemiriam agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT abuincarmen agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT baocaamanoaida agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT garciacaballerotomas agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT brozosvazquezelena agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT rodriguezlopezcarmela agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT cebeyvictor agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT palaciospatricia agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT cuevajuanf agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT lopezlopezrafael agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT costaclotilde agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT diazlagaresangel agenomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT rodriguezcasanovaaitor genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT costafraganicolas genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT castrocarballeiraclara genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT gonzalezcondemiriam genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT abuincarmen genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT baocaamanoaida genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT garciacaballerotomas genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT brozosvazquezelena genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT rodriguezlopezcarmela genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT cebeyvictor genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT palaciospatricia genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT cuevajuanf genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT lopezlopezrafael genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT costaclotilde genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer
AT diazlagaresangel genomewidecellfreednamethylationanalysisidentifiesanepisignatureassociatedwithmetastaticluminalbbreastcancer