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Updated: Jan 24, 2026
Generation and Culturing of High-Grade Serous Ovarian Cancer Patient-Derived Organoids
Published on: January 6, 2023
NECTIN4 (PVRL4) as Putative Therapeutic Target for a Specific Subtype of High Grade Serous Ovarian Cancer-An
Christine Bekos1, Besnik Muqaku2, Sabine Dekan3
1Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria. christine.bekos@meduniwien.ac.at.
Abstract:
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.
Insights
High Nectin 4 expression in ovarian cancer correlates with poor survival and immune changes. Targeting Nectin 4 with an antibody drug may offer a new therapy for peritoneal metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- High-grade serous ovarian cancer (HGSOC) with peritoneal involvement often has a poor prognosis.
- Targeted therapies are needed to address peritoneal metastasis in HGSOC.
Purpose of the Study:
- To identify a druggable target for peritoneal metastasis in HGSOC.
- To investigate the role of NECTIN4 as a potential therapeutic target.
Main Methods:
- Construction of a gene expression network to identify hub genes associated with peritoneal spread.
- Validation of protein expression using immunohistochemistry.
- Correlation analysis of deregulated pathways with omics data.
- Characterization of cell lines with high and low NECTIN4 expression.
Main Results:
- A gene cluster upregulated in miliary tumors with NECTIN4 as the hub gene was identified.
- High Nectin 4 protein expression correlated with unfavorable survival.
- Associations were found with reduced HLA and chromosome 22q11/12 gene expression, increased BCAM and Kallikrein expression, and altered immune cell populations (e.g., CD14+, NK cells).
Conclusions:
- NECTIN4 is a potential therapeutic target in HGSOC with peritoneal involvement.
- An anti-Nectin 4 antibody drug, currently in clinical trials, could be a candidate for targeted therapy in patients with extensive peritoneal disease.
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