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Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers
BACKGROUND: Screening for ovarian cancer (OC) in women at high risk consists of a combination of carbohydrate antigen 125 (CA125) and transvaginal ultrasound, despite their low sensitivity and specificity. This could be improved by the combination of several biomarkers, which has been shown in avera...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731824/ https://www.ncbi.nlm.nih.gov/pubmed/29244844 http://dx.doi.org/10.1371/journal.pone.0189641 |
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author | Gschwantler-Kaulich, Daphne Weingartshofer, Sigrid Rappaport-Fürhauser, Christine Zeilinger, Robert Pils, Dietmar Muhr, Daniela Braicu, Elena I. Kastner, Marie-Therese Tan, Yen Y. Semmler, Lorenz Sehouli, Jalid Singer, Christian F. |
author_facet | Gschwantler-Kaulich, Daphne Weingartshofer, Sigrid Rappaport-Fürhauser, Christine Zeilinger, Robert Pils, Dietmar Muhr, Daniela Braicu, Elena I. Kastner, Marie-Therese Tan, Yen Y. Semmler, Lorenz Sehouli, Jalid Singer, Christian F. |
author_sort | Gschwantler-Kaulich, Daphne |
collection | PubMed |
description | BACKGROUND: Screening for ovarian cancer (OC) in women at high risk consists of a combination of carbohydrate antigen 125 (CA125) and transvaginal ultrasound, despite their low sensitivity and specificity. This could be improved by the combination of several biomarkers, which has been shown in average risk patients but has not been investigated until now in female BRCA mutation carriers. METHODS: Using a multiplex, bead-based, immunoassay system, we analyzed the concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, CA125 and human epididymis antigen 4 in 26 healthy wild type women, 26 healthy BRCA1 mutation carriers, 28 wildtype OC patients and 26 OC patients with BRCA1 mutation. RESULTS: Using the ROC analysis, we found a high overall sensitivity of 94.3% in differentiating healthy controls from OC patients with comparable results in the wildtype subgroup (sensitivity 92.8%, AUC = 0.988; p = 5.2e-14) as well as in BRCA1 mutation carriers (sensitivity 95.2%, AUC = 0.978; p = 1.7e-15) at an overall specificity of 92.3%. The used algorithm also allowed to identify healthy BRCA1 mutation carriers when compared to healthy wildtype women (sensitivity 88.4%, specificity 80.7%, AUC = 0.895; p = 6e-08), while this was less pronounced in patients with OC (sensitivity 66.7%, specificity 67.8%, AUC = 0.724; p = 0.00065). CONCLUSION: We have developed an algorithm, which can differentiate between healthy women and OC patients and have for the first time shown, that such an algorithm can also be used in BRCA mutation carriers. To clarify a suggested benefit to the existing early detection program, large prospective trials with mainly early stage OC cases are warranted. |
format | Online Article Text |
id | pubmed-5731824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57318242017-12-22 Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers Gschwantler-Kaulich, Daphne Weingartshofer, Sigrid Rappaport-Fürhauser, Christine Zeilinger, Robert Pils, Dietmar Muhr, Daniela Braicu, Elena I. Kastner, Marie-Therese Tan, Yen Y. Semmler, Lorenz Sehouli, Jalid Singer, Christian F. PLoS One Research Article BACKGROUND: Screening for ovarian cancer (OC) in women at high risk consists of a combination of carbohydrate antigen 125 (CA125) and transvaginal ultrasound, despite their low sensitivity and specificity. This could be improved by the combination of several biomarkers, which has been shown in average risk patients but has not been investigated until now in female BRCA mutation carriers. METHODS: Using a multiplex, bead-based, immunoassay system, we analyzed the concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, CA125 and human epididymis antigen 4 in 26 healthy wild type women, 26 healthy BRCA1 mutation carriers, 28 wildtype OC patients and 26 OC patients with BRCA1 mutation. RESULTS: Using the ROC analysis, we found a high overall sensitivity of 94.3% in differentiating healthy controls from OC patients with comparable results in the wildtype subgroup (sensitivity 92.8%, AUC = 0.988; p = 5.2e-14) as well as in BRCA1 mutation carriers (sensitivity 95.2%, AUC = 0.978; p = 1.7e-15) at an overall specificity of 92.3%. The used algorithm also allowed to identify healthy BRCA1 mutation carriers when compared to healthy wildtype women (sensitivity 88.4%, specificity 80.7%, AUC = 0.895; p = 6e-08), while this was less pronounced in patients with OC (sensitivity 66.7%, specificity 67.8%, AUC = 0.724; p = 0.00065). CONCLUSION: We have developed an algorithm, which can differentiate between healthy women and OC patients and have for the first time shown, that such an algorithm can also be used in BRCA mutation carriers. To clarify a suggested benefit to the existing early detection program, large prospective trials with mainly early stage OC cases are warranted. Public Library of Science 2017-12-15 /pmc/articles/PMC5731824/ /pubmed/29244844 http://dx.doi.org/10.1371/journal.pone.0189641 Text en © 2017 Gschwantler-Kaulich et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gschwantler-Kaulich, Daphne Weingartshofer, Sigrid Rappaport-Fürhauser, Christine Zeilinger, Robert Pils, Dietmar Muhr, Daniela Braicu, Elena I. Kastner, Marie-Therese Tan, Yen Y. Semmler, Lorenz Sehouli, Jalid Singer, Christian F. Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers |
title | Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers |
title_full | Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers |
title_fullStr | Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers |
title_full_unstemmed | Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers |
title_short | Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers |
title_sort | diagnostic markers for the detection of ovarian cancer in brca1 mutation carriers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731824/ https://www.ncbi.nlm.nih.gov/pubmed/29244844 http://dx.doi.org/10.1371/journal.pone.0189641 |
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