{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:46:17Z","timestamp":1792431977400,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T00:00:00Z","timestamp":1558310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P28137"],"award-info":[{"award-number":["P28137"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank","doi-asserted-by":"publisher","award":["14595"],"award-info":[{"award-number":["14595"]}],"id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006727","name":"Hochschuljubil\u00e4umsstiftung der Stadt Wien","doi-asserted-by":"publisher","award":["H-317502\/2017"],"award-info":[{"award-number":["H-317502\/2017"]}],"id":[{"id":"10.13039\/501100006727","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2014scale free small world\u2014co-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\u2013already under clinical investigation\u2013could be a candidate for a targeted therapy in patients with extensive peritoneal involvement.<\/jats:p>","DOI":"10.3390\/cancers11050698","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T11:05:07Z","timestamp":1558350307000},"page":"698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["NECTIN4 (PVRL4) as Putative Therapeutic Target for a Specific Subtype of High Grade Serous Ovarian Cancer\u2014An Integrative Multi-Omics Approach"],"prefix":"10.3390","volume":"11","author":[{"given":"Christine","family":"Bekos","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Besnik","family":"Muqaku","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Dekan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Horvat","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Polterauer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4964-0642","authenticated-orcid":false,"given":"Christopher","family":"Gerner","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6760-949X","authenticated-orcid":false,"given":"Stefanie","family":"Aust","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8355-0977","authenticated-orcid":false,"given":"Dietmar","family":"Pils","sequence":"additional","affiliation":[{"name":"Section for Clinical Biometrics, Center for Medical Statistics, Informatics, and Intelligent Systems (CeMSIIS), Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Surgery, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1111\/j.1349-7006.2009.01204.x","article-title":"Gene expression profiling of advanced-stage serous ovarian cancers distinguishes novel subclasses and implicates ZEB2 in tumor progression and prognosis","volume":"100","author":"Yoshihara","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Crijns, A.P., Fehrmann, R.S., de Jong, S., Gerbens, F., Meersma, G.J., Klip, H.G., Hollema, H., Hofstra, R.M., te Meerman, G.J., and de Vries, E.G. 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