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Article

NECTIN4 (PVRL4) as Putative Therapeutic Target for a Specific Subtype of High Grade Serous Ovarian Cancer—An Integrative Multi-Omics Approach

1
Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria
2
Department of Analytical Chemistry, University of Vienna, 1090 Vienna, Austria
3
Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria
4
Section for Clinical Biometrics, Center for Medical Statistics, Informatics, and Intelligent Systems (CeMSIIS), Medical University of Vienna, 1090 Vienna, Austria
5
Department of Surgery, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 698; https://doi.org/10.3390/cancers11050698
Received: 8 April 2019 / Revised: 15 May 2019 / Accepted: 16 May 2019 / Published: 20 May 2019
(This article belongs to the Special Issue Targeting Solid Tumors)
In high grade serous ovarian cancer patients with peritoneal involvement and unfavorable outcome would benefit from targeted therapies. The aim of this study was to find a druggable target against peritoneal metastasis. We constructed a planar—scale free small world—co-association gene expression network and searched for clusters with hub-genes associated to peritoneal spread. Protein expression and impact was validated via immunohistochemistry and correlations of deregulated pathways with comprehensive omics data were used for biological interpretation. A cluster up-regulated in miliary tumors with NECTIN4 as hub-gene was identified and impact on survival validated. High Nectin 4 protein expression was associated with unfavorable survival and (i) reduced expression of HLA genes (mainly MHC I); (ii) with reduced expression of genes from chromosome 22q11/12; (iii) higher BCAM in ascites and in a high-scoring expression cluster; (iv) higher Kallikrein gene and protein expressions; and (v) substantial immunologic differences; locally and systemically; e.g., reduced CD14 positive cells and reduction of different natural killer cell populations. Each three cell lines with high (miliary) or low NECTIN4 expression (non-miliary) were identified. An anti-Nectin 4 antibody with a linked antineoplastic drug–already under clinical investigation–could be a candidate for a targeted therapy in patients with extensive peritoneal involvement. View Full-Text
Keywords: Nectin 4; NECTIN4; PVRL4; tumor spread; miliary or non-miliary; fallopian tube secretory epithelial cells (FTE); ovarian surface epithelial cells (OSE) Nectin 4; NECTIN4; PVRL4; tumor spread; miliary or non-miliary; fallopian tube secretory epithelial cells (FTE); ovarian surface epithelial cells (OSE)
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MDPI and ACS Style

Bekos, C.; Muqaku, B.; Dekan, S.; Horvat, R.; Polterauer, S.; Gerner, C.; Aust, S.; Pils, D. NECTIN4 (PVRL4) as Putative Therapeutic Target for a Specific Subtype of High Grade Serous Ovarian Cancer—An Integrative Multi-Omics Approach. Cancers 2019, 11, 698. https://doi.org/10.3390/cancers11050698

AMA Style

Bekos C, Muqaku B, Dekan S, Horvat R, Polterauer S, Gerner C, Aust S, Pils D. NECTIN4 (PVRL4) as Putative Therapeutic Target for a Specific Subtype of High Grade Serous Ovarian Cancer—An Integrative Multi-Omics Approach. Cancers. 2019; 11(5):698. https://doi.org/10.3390/cancers11050698

Chicago/Turabian Style

Bekos, Christine, Besnik Muqaku, Sabine Dekan, Reinhard Horvat, Stephan Polterauer, Christopher Gerner, Stefanie Aust, and Dietmar Pils. 2019. "NECTIN4 (PVRL4) as Putative Therapeutic Target for a Specific Subtype of High Grade Serous Ovarian Cancer—An Integrative Multi-Omics Approach" Cancers 11, no. 5: 698. https://doi.org/10.3390/cancers11050698

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