Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer |
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| Authors: | Sergio Marchini Robert Fruscio Luca Clivio Luca Beltrame Luca Porcu Ilaria Fuso Nerini Duccio Cavalieri Giovanna Chiorino Giorgio Cattoretti Costantino Mangioni Rodolfo Milani Valter Torri Chiara Romualdi Alberto Zambelli Michela Romano Mauro Signorelli Silvana di Giandomenico Maurizio D’Incalci |
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| Affiliation: | 1. Department of Oncology, Mario Negri Institute for Pharmacological Research, Milano, Italy;2. Clinic of Obstetrics and Gynecology, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy;3. Department of Pharmacology, University of Firenze, Italy;4. Research and Innovation Centre Edmund Mach Foundation San Michele all ‘Adige, Trento, Italy;5. Cancer Genomic Laboratory, Edo Tempia Foundation, Biella, Italy;6. Anatomo-Pathology Unit, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy;7. Department of Biology, University of Padova, Italy;8. IRCCS Fondazione S. Maugeri, Pavia, Italy;9. MaNGO Group, Milano, Italy |
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| Abstract: | BackgroundThe present study is aimed to identify genetic pathways correlated with chemoresistance in epithelial ovarian cancer (EOC).MethodsWe 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.ResultsIn 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.ConclusionSome genes involved in EMT were associated to overall or progression free survival, suggesting EMT as vital to the resistance mechanisms. |
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