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.
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.
Authors: Haiyan Zhu; Xiang Gu; Lu Xia; You Zhou; Hakim Bouamar; Junhua Yang; Xiaofei Ding; Christian Zwieb; Jianan Zhang; Andrew P Hinck; Lu-Zhe Sun; Xueqiong Zhu Journal: Clin Cancer Res Date: 2018-03-16 Impact factor: 12.531
Authors: Bernadette M Boac; Yin Xiong; Douglas C Marchion; Forough Abbasi; Stephen H Bush; Ingrid J Ramirez; Beman R Khulpateea; E Clair McClung; Amy L Berry; Nadim Bou Zgheib; Hye Sook Chon; Mian M Shahzad; Patricia L Judson; Robert M Wenham; Sachin M Apte; Anders E Berglund; Anthony M Magliocco; Johnathan M Lancaster Journal: Gynecol Oncol Date: 2015-12-28 Impact factor: 5.482
Authors: Laura D Hover; Christian D Young; Neil E Bhola; Andrew J Wilson; Dineo Khabele; Charles C Hong; Harold L Moses; Philip Owens Journal: Cancer Lett Date: 2015-07-30 Impact factor: 8.679