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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.1016955/full |
| _version_ | 1811234540646039552 |
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| author | Aitor Rodriguez-Casanova Aitor Rodriguez-Casanova Aitor Rodriguez-Casanova Nicolas Costa-Fraga Nicolas Costa-Fraga Clara Castro-Carballeira Miriam González-Conde Miriam González-Conde Carmen Abuin Aida Bao-Caamano Aida Bao-Caamano Tomás García-Caballero Elena Brozos-Vazquez Carmela Rodriguez-López Victor Cebey Patricia Palacios Juan F. Cueva Juan F. Cueva Rafael López-López Rafael López-López Rafael López-López Clotilde Costa Clotilde Costa Angel Díaz-Lagares Angel Díaz-Lagares |
| author_facet | Aitor Rodriguez-Casanova Aitor Rodriguez-Casanova Aitor Rodriguez-Casanova Nicolas Costa-Fraga Nicolas Costa-Fraga Clara Castro-Carballeira Miriam González-Conde Miriam González-Conde Carmen Abuin Aida Bao-Caamano Aida Bao-Caamano Tomás García-Caballero Elena Brozos-Vazquez Carmela Rodriguez-López Victor Cebey Patricia Palacios Juan F. Cueva Juan F. Cueva Rafael López-López Rafael López-López Rafael López-López Clotilde Costa Clotilde Costa Angel Díaz-Lagares Angel Díaz-Lagares |
| author_sort | Aitor Rodriguez-Casanova |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T11:38:05Z |
| format | Article |
| id | doaj.art-eed70f27ab04426b97329ccbc70f0e54 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T11:38:05Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-eed70f27ab04426b97329ccbc70f0e542022-12-22T03:34:47ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-10-011010.3389/fcell.2022.10169551016955A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancerAitor Rodriguez-Casanova0Aitor Rodriguez-Casanova1Aitor Rodriguez-Casanova2Nicolas Costa-Fraga3Nicolas Costa-Fraga4Clara Castro-Carballeira5Miriam González-Conde6Miriam González-Conde7Carmen Abuin8Aida Bao-Caamano9Aida Bao-Caamano10Tomás García-Caballero11Elena Brozos-Vazquez12Carmela Rodriguez-López13Victor Cebey14Patricia Palacios15Juan F. Cueva16Juan F. Cueva17Rafael López-López18Rafael López-López19Rafael López-López20Clotilde Costa21Clotilde Costa22Angel Díaz-Lagares23Angel Díaz-Lagares24Epigenomics Unit, Cancer Epigenomics, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainRoche-Chus Joint Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Santiago de Compostela, SpainUniversidade de Santiago de Compostela (USC), Santiago de Compostela, SpainEpigenomics Unit, Cancer Epigenomics, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainUniversidade de Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Oncology, Marqués de Valdecilla University Hospital, Santander, SpainRoche-Chus Joint Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Santiago de Compostela, SpainCentro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, Madrid, SpainRoche-Chus Joint Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Santiago de Compostela, SpainEpigenomics Unit, Cancer Epigenomics, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainUniversidade de Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Morphological Sciences, University of Santiago de Compostela and Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainCentro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, Madrid, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainRoche-Chus Joint Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Santiago de Compostela, SpainCentro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, Madrid, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainRoche-Chus Joint Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Santiago de Compostela, SpainCentro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, Madrid, SpainEpigenomics Unit, Cancer Epigenomics, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, SpainCentro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, Madrid, SpainBreast 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.https://www.frontiersin.org/articles/10.3389/fcell.2022.1016955/fullDNA methylationEPIC Arraycell-free DNAliquid biopsymetastasisluminal B |
| spellingShingle | Aitor Rodriguez-Casanova Aitor Rodriguez-Casanova Aitor Rodriguez-Casanova Nicolas Costa-Fraga Nicolas Costa-Fraga Clara Castro-Carballeira Miriam González-Conde Miriam González-Conde Carmen Abuin Aida Bao-Caamano Aida Bao-Caamano Tomás García-Caballero Elena Brozos-Vazquez Carmela Rodriguez-López Victor Cebey Patricia Palacios Juan F. Cueva Juan F. Cueva Rafael López-López Rafael López-López Rafael López-López Clotilde Costa Clotilde Costa Angel Díaz-Lagares Angel Díaz-Lagares A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer Frontiers in Cell and Developmental Biology DNA methylation EPIC Array cell-free DNA liquid biopsy metastasis luminal B |
| 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 | DNA methylation EPIC Array cell-free DNA liquid biopsy metastasis luminal B |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.1016955/full |
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