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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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 |
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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 |
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