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

S Marchini, R Fruscio, L Clivio, L Beltrame… - European journal of …, 2013 - Elsevier
European journal of cancer, 2013Elsevier
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 …
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 6months 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.
Elsevier