Project description:Despite a pathological complete response, risk-of-relapse remains a challenge for most of epithelial ovarian cancer (EOC) patients and an ad-hoc predictor can be a valuable clinical tool. We developed a 35 miRNAs-based predictor of Risk of Ovarian Cancer Relapse (MiROvaR) using a training set of patients from MITO-2 (Multicentre Italian Trials in Ovarian Cancer-2; Pignata S et al. J Clin Oncol. 2011 Sep 20). MiROvaR performance was confirmed in two independent validation cohorts.
Project description:Despite a pathological complete response, risk-of-relapse remains a challenge for most of epithelial ovarian cancer (EOC) patients and an ad-hoc predictor can be a valuable clinical tool. We developed a 35 miRNAs-based predictor of Risk of Ovarian Cancer Relapse (MiROvaR) using a training set of patients from MITO-2 (Multicentre Italian Trials in Ovarian Cancer-2; Pignata S et al. J Clin Oncol. 2011 Sep 20). MiROvaR performance was confirmed in two independent validation cohorts.
Project description:A major challenge in advanced-stage epithelial ovarian cancer (EOC) is prediction of chemoresistant relapse. Our aim was to identify a microRNA (miRNA) signature associated with early relapse in advanced-stage EOC patients. miRNA expression was assessed by microarray profiling in training (n = 55) and test (n = 30) sets selected on the basis of time to relapse (TTR), followed by internal quantitative reverse transcriptase-PCR validation on a set of 45 consecutive cases unselected for clinical response and external in silico validation on publicly available datasets. Thirty-two differentially expressed miRNAs in early vs. late relapsing patients were identified in the training set. In the test set, 8 of these, belonging to a cluster located on chrXq27.3, were down-modulated in early relapsing patients. Hierarchical clustering of the internal validation set according to chrXq27.3 miRNA expression associated low miRNA expression with shorter TTR (log-rank P=0.00074, HR 2.44). The cluster was an independent prognostic factor in both internal and external validation sets. Forced expression of chrXq27.3-cluster selected miRNAs in human EOC cellular models was associated to reduction of cell proliferation and increased sensitivity to cisplatin. The role of down-modulation of the chrXq27.3 miRNA cluster in early relapse of advanced-stage EOC patients and its association to a reduced sensitivity to chemotherapeutic treatments warrant further investigation.
Project description:A set of 45 surgical specimens has been profiled for miRNA expression to validate miRNA alterations associated to early relapse in advanced stage ovarian cancer patients.
Project description:A set of 45 surgical specimens has been profiled for miRNA expression to validate miRNA alterations associated to early relapse in advanced stage ovarian cancer patients. Fresh frozen samples were collected from a series of consecutive patients with high-grade advanced stage ovarian cancer who underwent primary surgery at INT-Milan. After surgery all patients received postoperative platinum-based chemotherapy. All patients signed an Institutional Review Board approved consent for bio-banking, clinical data collection and molecular analysis. Clinical codes: Histotype: according to WHO classification guidelines Stage: according to International Federation of Gynecological and Obstetrics (FIGO) guidelines Grading: according to WHO classification guidelines Debulking: NED: not evident disease; mRD: minimal residual disease; GRD: gross residual disease Therapy code: P: Platinum without taxanes; PT: Platinum/paclitaxel
Project description:The aim of our study is to develop a miRNA marker panel prognostic of 5-year survival in early-stage OSCC patients. We assessed differential expression of miRNAs genome-wide via deep sequencing in 100 tumor tissue samples. We also attempted to identify deregulated miRNA expression signatures that may serve as the prognostic markers.