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


CONCLUSIONS
Some genes involved in EMT were associated to overall or progression free survival, suggesting EMT as vital to the resistance mechanisms.
Department of Oncology, Mario Negri Institute for Pharmacological Research, Milano, Italy.
Sergio
S
Marchini
Robert
R
Fruscio
Luca
L
Clivio
Luca
L
Beltrame
Luca
L
Porcu
Ilaria
I
Fuso Nerini
Duccio
D
Cavalieri
Giovanna
G
Chiorino
Giorgio
G
Cattoretti
Costantino
C
Mangioni
Rodolfo
R
Milani
Valter
V
Torri
Chiara
C
Romualdi
Alberto
A
Zambelli
Michela
M
Romano
Mauro
M
Signorelli
Silvana
S
di Giandomenico
Maurizio
M
D'Incalci
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D015398:Signal Transduction; D016896:Treatment Outcome
D009944:Organoplatinum Compounds