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A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA

Background: Breast cancer (BrC) is the most frequent neoplasm in women. New biomarkers, including aberrant DNA methylation, may improve BrC management. Herein, we evaluated the detection and prognostic performance of seven genes’ promoter methylation (APC, BRCA1, CCND2, FOXA1, PSAT1, RASSF1A and SCG...

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Autores principales: Salta, Sofia, P. Nunes, Sandra, Fontes-Sousa, Mário, Lopes, Paula, Freitas, Micaela, Caldas, Margarida, Antunes, Luís, Castro, Fernando, Antunes, Pedro, Palma de Sousa, Susana, Henrique, Rui, Jerónimo, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262630/
https://www.ncbi.nlm.nih.gov/pubmed/30405052
http://dx.doi.org/10.3390/jcm7110420
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author Salta, Sofia
P. Nunes, Sandra
Fontes-Sousa, Mário
Lopes, Paula
Freitas, Micaela
Caldas, Margarida
Antunes, Luís
Castro, Fernando
Antunes, Pedro
Palma de Sousa, Susana
Henrique, Rui
Jerónimo, Carmen
author_facet Salta, Sofia
P. Nunes, Sandra
Fontes-Sousa, Mário
Lopes, Paula
Freitas, Micaela
Caldas, Margarida
Antunes, Luís
Castro, Fernando
Antunes, Pedro
Palma de Sousa, Susana
Henrique, Rui
Jerónimo, Carmen
author_sort Salta, Sofia
collection PubMed
description Background: Breast cancer (BrC) is the most frequent neoplasm in women. New biomarkers, including aberrant DNA methylation, may improve BrC management. Herein, we evaluated the detection and prognostic performance of seven genes’ promoter methylation (APC, BRCA1, CCND2, FOXA1, PSAT1, RASSF1A and SCGB3A1). Methods: Methylation levels were assessed in primary BrC tissues by quantitative methylation-specific polymerase chain reaction (QMSP) and in circulating cell-free DNA (ccfDNA) by multiplex QMSP from two independent cohorts of patients (Cohort #1, n = 137; and Cohort #2, n = 44). Receiver operating characteristic (ROC) curves were constructed, and log-rank test and Cox regression were performed to assess the prognostic value of genes’ methylation levels. Results: The gene-panel APC, FOXA1, RASSF1A, SCGB3A1 discriminated normal from cancerous tissue with high accuracy (95.55%). In multivariable analysis, high PSAT1-methylation levels [>percentile 75 (P75)] associated with longer disease-free survival, whereas higher FOXA1-methylation levels (>P75) associated with shorter disease-specific survival. The best performing panel in ccfDNA (APC, FOXA1 and RASSF1A) disclosed a sensitivity, specificity and accuracy over 70%. Conclusions: This approach enables BrC accurate diagnosis and prognostic stratification in tissue samples, and allows for early detection in liquid biopsies, thus suggesting a putative value for patient management.
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spelling pubmed-62626302018-12-03 A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA Salta, Sofia P. Nunes, Sandra Fontes-Sousa, Mário Lopes, Paula Freitas, Micaela Caldas, Margarida Antunes, Luís Castro, Fernando Antunes, Pedro Palma de Sousa, Susana Henrique, Rui Jerónimo, Carmen J Clin Med Article Background: Breast cancer (BrC) is the most frequent neoplasm in women. New biomarkers, including aberrant DNA methylation, may improve BrC management. Herein, we evaluated the detection and prognostic performance of seven genes’ promoter methylation (APC, BRCA1, CCND2, FOXA1, PSAT1, RASSF1A and SCGB3A1). Methods: Methylation levels were assessed in primary BrC tissues by quantitative methylation-specific polymerase chain reaction (QMSP) and in circulating cell-free DNA (ccfDNA) by multiplex QMSP from two independent cohorts of patients (Cohort #1, n = 137; and Cohort #2, n = 44). Receiver operating characteristic (ROC) curves were constructed, and log-rank test and Cox regression were performed to assess the prognostic value of genes’ methylation levels. Results: The gene-panel APC, FOXA1, RASSF1A, SCGB3A1 discriminated normal from cancerous tissue with high accuracy (95.55%). In multivariable analysis, high PSAT1-methylation levels [>percentile 75 (P75)] associated with longer disease-free survival, whereas higher FOXA1-methylation levels (>P75) associated with shorter disease-specific survival. The best performing panel in ccfDNA (APC, FOXA1 and RASSF1A) disclosed a sensitivity, specificity and accuracy over 70%. Conclusions: This approach enables BrC accurate diagnosis and prognostic stratification in tissue samples, and allows for early detection in liquid biopsies, thus suggesting a putative value for patient management. MDPI 2018-11-07 /pmc/articles/PMC6262630/ /pubmed/30405052 http://dx.doi.org/10.3390/jcm7110420 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Salta, Sofia
P. Nunes, Sandra
Fontes-Sousa, Mário
Lopes, Paula
Freitas, Micaela
Caldas, Margarida
Antunes, Luís
Castro, Fernando
Antunes, Pedro
Palma de Sousa, Susana
Henrique, Rui
Jerónimo, Carmen
A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA
title A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA
title_full A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA
title_fullStr A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA
title_full_unstemmed A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA
title_short A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA
title_sort dna methylation-based test for breast cancer detection in circulating cell-free dna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262630/
https://www.ncbi.nlm.nih.gov/pubmed/30405052
http://dx.doi.org/10.3390/jcm7110420
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