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Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer

Detection of epithelial ovarian cancer (EOC) poses a critical medical challenge. However, novel biomarkers for diagnosis remain to be discovered. Therefore, innovative approaches are of the utmost importance for patient outcome. Here, we present a concept for blood-based biomarker discovery, investi...

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Autores principales: Kulbe, Hagen, Otto, Raik, Darb-Esfahani, Silvia, Lammert, Hedwig, Abobaker, Salem, Welsch, Gabriele, Chekerov, Radoslav, Schäfer, Reinhold, Dragun, Duska, Hummel, Michael, Leser, Ulf, Sehouli, Jalid, Braicu, Elena Ioana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678810/
https://www.ncbi.nlm.nih.gov/pubmed/31336942
http://dx.doi.org/10.3390/cells8070713
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author Kulbe, Hagen
Otto, Raik
Darb-Esfahani, Silvia
Lammert, Hedwig
Abobaker, Salem
Welsch, Gabriele
Chekerov, Radoslav
Schäfer, Reinhold
Dragun, Duska
Hummel, Michael
Leser, Ulf
Sehouli, Jalid
Braicu, Elena Ioana
author_facet Kulbe, Hagen
Otto, Raik
Darb-Esfahani, Silvia
Lammert, Hedwig
Abobaker, Salem
Welsch, Gabriele
Chekerov, Radoslav
Schäfer, Reinhold
Dragun, Duska
Hummel, Michael
Leser, Ulf
Sehouli, Jalid
Braicu, Elena Ioana
author_sort Kulbe, Hagen
collection PubMed
description Detection of epithelial ovarian cancer (EOC) poses a critical medical challenge. However, novel biomarkers for diagnosis remain to be discovered. Therefore, innovative approaches are of the utmost importance for patient outcome. Here, we present a concept for blood-based biomarker discovery, investigating both epithelial and specifically stromal compartments, which have been neglected in search for novel candidates. We queried gene expression profiles of EOC including microdissected epithelium and adjacent stroma from benign and malignant tumours. Genes significantly differentially expressed within either the epithelial or the stromal compartments were retrieved. The expression of genes whose products are secreted yet absent in the blood of healthy donors were validated in tissue and blood from patients with pelvic mass by NanoString analysis. Results were confirmed by the comprehensive gene expression database, CSIOVDB (Ovarian cancer database of Cancer Science Institute Singapore). The top 25% of candidate genes were explored for their biomarker potential, and twelve were able to discriminate between benign and malignant tumours on transcript levels (p < 0.05). Among them T-cell differentiation protein myelin and lymphocyte (MAL), aurora kinase A (AURKA), stroma-derived candidates versican (VCAN), and syndecan-3 (SDC), which performed significantly better than the recently reported biomarker fibroblast growth factor 18 (FGF18) to discern malignant from benign conditions. Furthermore, elevated MAL and AURKA expression levels correlated significantly with a poor prognosis. We identified promising novel candidates and found the stroma of EOC to be a suitable compartment for biomarker discovery.
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spelling pubmed-66788102019-08-19 Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer Kulbe, Hagen Otto, Raik Darb-Esfahani, Silvia Lammert, Hedwig Abobaker, Salem Welsch, Gabriele Chekerov, Radoslav Schäfer, Reinhold Dragun, Duska Hummel, Michael Leser, Ulf Sehouli, Jalid Braicu, Elena Ioana Cells Article Detection of epithelial ovarian cancer (EOC) poses a critical medical challenge. However, novel biomarkers for diagnosis remain to be discovered. Therefore, innovative approaches are of the utmost importance for patient outcome. Here, we present a concept for blood-based biomarker discovery, investigating both epithelial and specifically stromal compartments, which have been neglected in search for novel candidates. We queried gene expression profiles of EOC including microdissected epithelium and adjacent stroma from benign and malignant tumours. Genes significantly differentially expressed within either the epithelial or the stromal compartments were retrieved. The expression of genes whose products are secreted yet absent in the blood of healthy donors were validated in tissue and blood from patients with pelvic mass by NanoString analysis. Results were confirmed by the comprehensive gene expression database, CSIOVDB (Ovarian cancer database of Cancer Science Institute Singapore). The top 25% of candidate genes were explored for their biomarker potential, and twelve were able to discriminate between benign and malignant tumours on transcript levels (p < 0.05). Among them T-cell differentiation protein myelin and lymphocyte (MAL), aurora kinase A (AURKA), stroma-derived candidates versican (VCAN), and syndecan-3 (SDC), which performed significantly better than the recently reported biomarker fibroblast growth factor 18 (FGF18) to discern malignant from benign conditions. Furthermore, elevated MAL and AURKA expression levels correlated significantly with a poor prognosis. We identified promising novel candidates and found the stroma of EOC to be a suitable compartment for biomarker discovery. MDPI 2019-07-12 /pmc/articles/PMC6678810/ /pubmed/31336942 http://dx.doi.org/10.3390/cells8070713 Text en © 2019 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
Kulbe, Hagen
Otto, Raik
Darb-Esfahani, Silvia
Lammert, Hedwig
Abobaker, Salem
Welsch, Gabriele
Chekerov, Radoslav
Schäfer, Reinhold
Dragun, Duska
Hummel, Michael
Leser, Ulf
Sehouli, Jalid
Braicu, Elena Ioana
Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer
title Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer
title_full Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer
title_fullStr Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer
title_full_unstemmed Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer
title_short Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer
title_sort discovery and validation of novel biomarkers for detection of epithelial ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678810/
https://www.ncbi.nlm.nih.gov/pubmed/31336942
http://dx.doi.org/10.3390/cells8070713
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