Bibliographic Details
| Title: |
Low Expression of Claudin-7 as Potential Predictor of Distant Metastases in High-Grade Serous Ovarian Carcinoma Patients |
| Authors: |
Chiara Romani, Valentina Zizioli, Marco Silvestri, Laura Ardighieri, Mattia Bugatti, Michela Corsini, Paola Todeschini, Sergio Marchini, Maurizio D'Incalci, Laura Zanotti, Antonella Ravaggi, Fabio Facchetti, Angela Gambino, Franco Odicino, Enrico Sartori, Alessandro Davide Santin, Stefania Mitola, Eliana Bignotti, Stefano Calza |
| Source: |
Frontiers in Oncology, Vol 10 (2020) |
| Publisher Information: |
Frontiers Media S.A., 2020. |
| Publication Year: |
2020 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
high grade serous ovarian carcinoma, fallopian tube epithelium, claudins, distant metastases, hematogenous spread, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
High-grade serous ovarian carcinoma (HGSOC) usually spreads directly into the peritoneal cavity following a transcoelomic dissemination route, although distant hematogenous metastasis exist and have been reported. However, no tumor markers can currently predict the risk of distant metastases in HGSOC. Claudins, belonging to tight-junction proteins, are dysregulated in HGSOC and functionally related to cancer progression. Here we analyzed claudin-3, -4, and -7 expression as potential markers of distant metastases. Using quantitative RT-PCR and immunohistochemistry we assessed the expression of claudins in primary HGSOC tissues, normal ovarian, and normal fallopian tube epithelia and correlated it with clinicopathological features, including the site of metastasis and the route of dissemination. Gene set enrichment analysis was performed on microarray-generated gene expression data to investigate key pathways in patients with distant metastases. We found the overall expression level of claudin-3, -4, and -7 mRNA decreased in HGSOC compared to normal tubal epithelium, currently considered the potential site of origin of many HGSOC. The reduced expression of claudin-7 is significantly associated with the development of distant metastases (p = 0.016), mainly by hematogenous route (p = 0.025). In patients with diminished expression of claudin-7, immunohistochemical staining revealed a heterogeneous pattern of membranous staining with discontinuous expression of claudin-7 along the cell border, indicative of a dischoesive architecture. The estimated reduction in the probability of distant disease is of 39% per unit increase in the level of claudin-7 (p = 0.03). Genes involved in epithelial to mesenchymal transition, hypoxia, and angiogenesis processes resulted strongly associated to hematogenous recurrence. Our data suggest a potential role of claudin-7 in discriminating distant metastatic events in HGSOC patients. The quantification of its expression levels could be a useful tool to identify patient deserving a personalized follow-up in terms of clinical and radiological assessment. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2234-943X |
| Relation: |
https://www.frontiersin.org/article/10.3389/fonc.2020.01287/full; https://doaj.org/toc/2234-943X |
| DOI: |
10.3389/fonc.2020.01287 |
| Access URL: |
https://doaj.org/article/8a3b8f139a7a4efa94b6ab8f116c19a7 |
| Accession Number: |
edsdoj.8a3b8f139a7a4efa94b6ab8f116c19a7 |
| Database: |
Directory of Open Access Journals |
