Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer
Significant evidence has accumulated that DNA-methylation of the paired-like homeodomain transcription factor 2 (PITX2) gene can serve as a prognostic and predictive biomarker in breast cancer. PITX2 DNA-methylation data have been obtained so far from microarray and polymerase chain reaction (PCR)-b...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237923/ https://www.ncbi.nlm.nih.gov/pubmed/30442983 http://dx.doi.org/10.1038/s41598-018-34919-1 |
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author | Schricker, Gabriele Napieralski, Rudolf Noske, Aurelia Piednoir, Elodie Manner, Olivia Schüren, Elisabeth Lauber, Jürgen Perkins, Jonathan Magdolen, Viktor Schmitt, Manfred Ulm, Kurt Weichert, Wilko Kiechle, Marion Martens, John W. M. Wilhelm, Olaf G. |
author_facet | Schricker, Gabriele Napieralski, Rudolf Noske, Aurelia Piednoir, Elodie Manner, Olivia Schüren, Elisabeth Lauber, Jürgen Perkins, Jonathan Magdolen, Viktor Schmitt, Manfred Ulm, Kurt Weichert, Wilko Kiechle, Marion Martens, John W. M. Wilhelm, Olaf G. |
author_sort | Schricker, Gabriele |
collection | PubMed |
description | Significant evidence has accumulated that DNA-methylation of the paired-like homeodomain transcription factor 2 (PITX2) gene can serve as a prognostic and predictive biomarker in breast cancer. PITX2 DNA-methylation data have been obtained so far from microarray and polymerase chain reaction (PCR)-based research tests. The availability of an analytically validated in vitro methylation-specific real-time PCR assay format (therascreen PITX2 RGQ PCR assay) intended for the determination of the percent methylation ratio (PMR) in the (PITX2) promoter 2 prompted us to investigate whether the clinical performance of these different assay systems generate comparable clinical outcome data. Mathematically converted microarray data of a previous breast cancer study (n = 204) into PMR values leads to a PITX2 cut-off value at PMR 14.73. Recalculation of the data to experimentally equivalent PMRs with the PCR PITX2 assay leads to a cut-off value at PMR 12 with the highest statistical significance. This cut-off predicts outcome of high-risk breast cancer patients to adjuvant anthracycline-based chemotherapy (n = 204; Hazard Ratio 2.48; p < 0.001) comparable to microarray generated results (n = 204; Hazard ratio 2.32; p < 0.0001). The therascreen PITX2 RGQ PCR assay is an analytically validated test with high reliability and robustness and predicts outcome of high-risk breast cancer patients to anthracycline-based chemotherapy. |
format | Online Article Text |
id | pubmed-6237923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62379232018-11-23 Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer Schricker, Gabriele Napieralski, Rudolf Noske, Aurelia Piednoir, Elodie Manner, Olivia Schüren, Elisabeth Lauber, Jürgen Perkins, Jonathan Magdolen, Viktor Schmitt, Manfred Ulm, Kurt Weichert, Wilko Kiechle, Marion Martens, John W. M. Wilhelm, Olaf G. Sci Rep Article Significant evidence has accumulated that DNA-methylation of the paired-like homeodomain transcription factor 2 (PITX2) gene can serve as a prognostic and predictive biomarker in breast cancer. PITX2 DNA-methylation data have been obtained so far from microarray and polymerase chain reaction (PCR)-based research tests. The availability of an analytically validated in vitro methylation-specific real-time PCR assay format (therascreen PITX2 RGQ PCR assay) intended for the determination of the percent methylation ratio (PMR) in the (PITX2) promoter 2 prompted us to investigate whether the clinical performance of these different assay systems generate comparable clinical outcome data. Mathematically converted microarray data of a previous breast cancer study (n = 204) into PMR values leads to a PITX2 cut-off value at PMR 14.73. Recalculation of the data to experimentally equivalent PMRs with the PCR PITX2 assay leads to a cut-off value at PMR 12 with the highest statistical significance. This cut-off predicts outcome of high-risk breast cancer patients to adjuvant anthracycline-based chemotherapy (n = 204; Hazard Ratio 2.48; p < 0.001) comparable to microarray generated results (n = 204; Hazard ratio 2.32; p < 0.0001). The therascreen PITX2 RGQ PCR assay is an analytically validated test with high reliability and robustness and predicts outcome of high-risk breast cancer patients to anthracycline-based chemotherapy. Nature Publishing Group UK 2018-11-15 /pmc/articles/PMC6237923/ /pubmed/30442983 http://dx.doi.org/10.1038/s41598-018-34919-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Schricker, Gabriele Napieralski, Rudolf Noske, Aurelia Piednoir, Elodie Manner, Olivia Schüren, Elisabeth Lauber, Jürgen Perkins, Jonathan Magdolen, Viktor Schmitt, Manfred Ulm, Kurt Weichert, Wilko Kiechle, Marion Martens, John W. M. Wilhelm, Olaf G. Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer |
title | Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer |
title_full | Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer |
title_fullStr | Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer |
title_full_unstemmed | Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer |
title_short | Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer |
title_sort | clinical performance of an analytically validated assay in comparison to microarray technology to assess pitx2 dna-methylation in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237923/ https://www.ncbi.nlm.nih.gov/pubmed/30442983 http://dx.doi.org/10.1038/s41598-018-34919-1 |
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