title: Evaluation of Prognostic and Predictive Significance of Circulating MicroRNAs in Ovarian Cancer Patients.
abstract: Ovarian cancer patients are recognized with poor prognosis. This study aimed to identify microRNAs in plasma for predicting response to treatment and outcome. We have investigated microRNAs in plasma from ovarian cancer patients enrolled in a large multicenter study (ICON7), investigating the effect of adding bevacizumab to standard chemotherapy in patients diagnosed with epithelial ovarian cancer. Patients with different histology, grade, and FIGO stages were included (n= 207) in this study. Screening of 754 unique microRNAs was performed in the discovery phase (n= 91) using TaqMan Low Density Arrays. The results were validated using single assays and RT-qPCR. Low levels of miR-200b, miR-1274A (tRNALys5), and miR-141 were significantly associated with better survival, confirmed with log-rank test in the validation set. The level of miR-1274A (tRNALys5) correlated with outcome was especially pronounced in the high-grade serous tumors. Interestingly, low level of miR-200c was associated with 5-month prolongation of PFS when treated with bevacizumab compared to standard chemotherapy. We found prognostic significance of miR-200b, miR-141, and miR-1274A (tRNALys5) in all histological types, where miR-1274A (tRNALys5) may be a specific marker in high-grade serous tumors. The level of miR-200c may be predictive of effect of treatment with bevacizumab. However, this needs further validation.
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
authors.forename: Ann Rita
authors.identifier: 0000-0003-1223-7948
authors.initials: AR
authors.lastname: Halvorsen
authors.affiliation: Department of Gynecologic Oncology, Institute for Cancer Genetics and Informatics and University of Oslo, Oslo, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kristensen
authors.affiliation: MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Embleton
authors.affiliation: DOCs International, Buckinghamshire, UK.
authors.forename: Cybil
authors.initials: C
authors.lastname: Adusei
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain; Department of Medical Sciences, Medical School, University of Girona, Girona, Spain.
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Barretina-Ginesta
authors.affiliation: Medical Oncology, Royal Prince Alfred Hospital and Concord Repatriation General Hospital and Chris O'Brien Lifehouse, Sydney, NSW, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Beale
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway; Department of Oncology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
authors.forename: Åslaug
authors.identifier: 0000-0002-5520-0275
authors.initials: Å
authors.lastname: Helland
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel