TY - JOUR
T1 - Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer
AU - Marchini, Sergio
AU - Fruscio, Robert
AU - Clivio, Luca
AU - Beltrame, Luca
AU - Porcu, Luca
AU - Nerini, Ilaria Fuso
AU - Cavalieri, Duccio
AU - Chiorino, Giovanna
AU - Cattoretti, Giorgio
AU - Mangioni, Costantino
AU - Milani, Rodolfo
AU - Torri, Valter
AU - Romualdi, Chiara
AU - Zambelli, Alberto
AU - Romano, Michela
AU - Signorelli, Mauro
AU - Giandomenico, Silvana Di
AU - D'Incalci, Maurizio
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Epithelial ovarian cancer
KW - Epithelial to mesenchymal transition
KW - Platinum-resistance
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U2 - 10.1016/j.ejca.2012.06.026
DO - 10.1016/j.ejca.2012.06.026
M3 - Article
C2 - 22897840
AN - SCOPUS:84872114095
VL - 49
SP - 520
EP - 530
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 2
ER -