Bibliographic Details
| Title: |
EM-transcriptomic signature predicts drug response in advanced stages of high-grade serous ovarian carcinoma based on ascites-derived primary cultures |
| Authors: |
Diana-Roxana Constantinescu, Andrei Sorop, Alina-Veronica Ghionescu, Daniela Lixandru, Vlad Herlea, Nicolae Bacalbasa, Simona Olimpia Dima |
| Source: |
Frontiers in Pharmacology, Vol 15 (2024) |
| Publisher Information: |
Frontiers Media S.A., 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
high-grade serous ovarian carcinoma, ascites-derived primary cultures, transcriptomic signature, chemoresistance, epithelial–mesenchymal transition, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
Introduction: High-grade serous ovarian carcinoma (HGSOC) remains a medical challenge despite considerable improvements in the treatment. Unfortunately, over 75% of patients have already metastasized at the time of diagnosis. Advances in understanding the mechanisms underlying how ascites cause chemoresistance are urgently needed to derive novel therapeutic strategies. This study aimed to identify the molecular markers involved in drug sensitivity and highlight the use of ascites as a potential model to investigate HGSOC treatment options.Methods: After conducting an in silico analysis, eight epithelial–mesenchymal (EM)-associated genes related to chemoresistance were identified. To evaluate differences in EM-associated genes in HGSOC samples, we analyzed ascites-derived HGSOC primary cell culture (AS), tumor (T), and peritoneal nodule (NP) samples. Moreover, in vitro experiments were employed to measure tumor cell proliferation and cell migration in AS, following treatment with doxorubicin (DOX) and cisplatin (CIS) and expression of these markers.Results: Our results showed that AS exhibits a mesenchymal phenotype compared to tumor and peritoneal nodule samples. Moreover, DOX and CIS treatment leads to an invasive-intermediate epithelial-to-mesenchymal transition (EMT) state of the AS by different EM-associated marker expression. For instance, the treatment of AS showed that CDH1 and GATA6 decreased after CIS exposure and increased after DOX treatment. On the contrary, the expression of KRT18 has an opposite pattern.Conclusion: Taken together, our study reports a comprehensive investigation of the EM-associated genes after drug exposure of AS. Exploring ascites and their associated cellular and soluble components is promising for understanding the HGSOC progression and treatment response at a personalized level. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1663-9812 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fphar.2024.1363142/full; https://doaj.org/toc/1663-9812 |
| DOI: |
10.3389/fphar.2024.1363142 |
| Access URL: |
https://doaj.org/article/bc747244f93340c796da098210de9b56 |
| Accession Number: |
edsdoj.bc747244f93340c796da098210de9b56 |
| Database: |
Directory of Open Access Journals |
