Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer

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• 作者：Sergio Marchini^a ; ^j ; Robert Fruscio^b ; ⁱ ; ^j ; Luca Clivio^a ; ^j ; Luca Beltrame^a ; ^j ; Luca Porcu^a ; Ilaria Fuso Nerini^a ; Duccio Cavalieri^c ; ^d ; Giovanna Chiorino^e ; Giorgio Cattoretti^f ; Costantino Mangioni^b ; Rodolfo Milani^b ; Valter Torri^a ; Chiara Romualdi^g ; Alberto Zambelli^h ; Michela Romano^a ; Mauro Signorelli^b ; Silvana di Giandomenico^a ; Maurizio D’ ; Incalci^a ; ⁱ ; ^{maurizio.dincalci@marionegri.it}
• 关键词：Epithelial ovarian cancer ; Platinum-resistance ; Epithelial to mesenchymal transition
• 刊名：European Journal of Cancer
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：49
• 期：2
• 页码：520-530
• 全文大小：1117 K

文摘

Background

The present study is aimed to identify genetic pathways correlated with chemoresistance in epithelial ovarian cancer (EOC).

Methods

We compared the molecular profiles of 23 tumour biopsies of stage III-IV (training set) at primary surgery, before chemotherapy, to the profile from the same patients at second surgery, after several lines of platinum (Pt)-based chemotherapy when the tumours were resistant. In the hypothesis that identified markers were related to Pt-resistance and to prognosis, we validated this signature in 52 EOC taken at primary surgery (validation set) selected to be either very sensitive to the first line therapy, i.e. not relapsing before one year from the end of therapy, or resistant, i.e. relapsing within 6 months from the end of therapy.

Results

In the training set, we identified a resistance signature indicative of the activation of epithelial to mesenchymal transition (EMT) by transforming growth factor (TGF)-beta pathway. We then validated this signature in 52 EOC taken at primary surgery (validation set). Some genes involved in EMT, such as BMP and activin membrane-bound inhibitor (BAMBI), and mir-141 resulted in association with overall or progression free survival.

Conclusion

Some genes involved in EMT were associated to overall or progression free survival, suggesting EMT as vital to the resistance mechanisms.