EM-transcriptomic signature predicts drug response in advanced stages of high-grade serous ovarian carcinoma based on ascites-derived primary cultures

基于腹水来源的原代培养物的 EM 转录组特征预测晚期高级别浆液性卵巢癌的药物反应

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作者:Diana-Roxana Constantinescu #, Andrei Sorop #, Alina-Veronica Ghionescu #, Daniela Lixandru, Vlad Herlea, Nicolae Bacalbasa, Simona Olimpia Dima

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.

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.

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