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Open AccessArticle

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

1
Tumourbank Ovarian Cancer Network, 13353 Berlin, Germany
2
Department of Gynaecology, European Competence Center for Ovarian Cancer, Campus Virchow Clinic, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany
3
Institute for Computer Sciences, Humboldt-Universität zu Berlin, 12489 Berlin, Germany
4
Insititute for Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
5
German Cancer Consortium (DKTK), Partner site Berlin, 10117 Berlin, Germany
6
Department of Nephrology and Transplantation, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany
*
Author to whom correspondence should be addressed.
Authors contributed equally to this work.
Cells 2019, 8(7), 713; https://doi.org/10.3390/cells8070713
Received: 8 May 2019 / Revised: 5 July 2019 / Accepted: 10 July 2019 / Published: 12 July 2019
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: 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, 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. View Full-Text
Keywords: biomarker discovery; ovarian cancer; tumour microenvironment; differential expression biomarker discovery; ovarian cancer; tumour microenvironment; differential expression
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MDPI and ACS Style

Kulbe, H.; Otto, R.; Darb-Esfahani, S.; Lammert, H.; Abobaker, S.; Welsch, G.; Chekerov, R.; Schäfer, R.; Dragun, D.; Hummel, M.; Leser, U.; Sehouli, J.; Braicu, E.I. Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer. Cells 2019, 8, 713. https://doi.org/10.3390/cells8070713

AMA Style

Kulbe H, Otto R, Darb-Esfahani S, Lammert H, Abobaker S, Welsch G, Chekerov R, Schäfer R, Dragun D, Hummel M, Leser U, Sehouli J, Braicu EI. Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer. Cells. 2019; 8(7):713. https://doi.org/10.3390/cells8070713

Chicago/Turabian Style

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 I. 2019. "Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer" Cells 8, no. 7: 713. https://doi.org/10.3390/cells8070713

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