Review MicroRNAs as prognostic markers in ovarian cancer Marta Llauradó a,b,1 , Blanca Majem b,1 , Tatiana Altadill b , Lucia Lanau b , Josep Castellví c , Jose Luis Sánchez-Iglesias d , Silvia Cabrera d , Javier De la Torre d , Berta Díaz-Feijoo d , Asuncion Pérez-Benavente d , Eva Colás b , Mireia Olivan b , Andreas Doll b , Francesc Alameda e , Xavier Matias-Guiu f , Gema Moreno-Bueno g , Mark S Carey h , Josep Maria Del Campo i , Antonio Gil-Moreno d,j , Jaume Reventós b,j,k,l,⇑ , Marina Rigau b a Faculty of Medicine, University of British Columbia, Vancouver, Canada b Research Unit in Biomedicine and Translational Oncology, Vall Hebron Research Institute University Hospital, Barcelona, Spain c Department of Pathology, Vall Hebron University Hospital, Barcelona, Spain d Department of Gynecological Oncology, Vall Hebron University Hospital, Barcelona, Spain e Department of Pathology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain f Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain g Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), IdiPAZ, 28029, Madrid, Spain & Fundación MD Anderson Internacional, 28033 Madrid, Spain h Division of Gynecologic Oncology, University of British Columbia and BC Cancer Agency, Vancouver, BC, Canada i Division of Gynecology and Head and Neck, Department of Oncology, Vall Hebron University Hospital, Barcelona, Spain j Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain k Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, Barcelona, Spain l IDIBELL- Bellvitge Biomedical Research Institute, Barcelona, Spain article info Article history: Received 5 December 2013 Received in revised form 9 February 2014 Accepted 25 March 2014 Available online 18 April 2014 Keywords: Ovarian cancer Chemotherapy Tumor resistance Prediction Prognosis miRNAs abstract Ovarian cancer (OC) is the most lethal gynecological malignancy among women. Over 70% of women with OC are diagnosed in advanced stages and most of these cases are incurable. Although most patients respond well to primary chemotherapy, tumors become resistant to treatment. Mechanisms of chemore- sistance in cancer cells may be associated with mutational events and/or alterations of gene expression through epigenetic events. Although focusing on known genes has already yielded new information, pre- viously unknown non-coding RNAs, such as microRNAs (miRNAs), also lead insight into the biology of chemoresistance. In this review we summarize the current evidence examining the role of miRNAs as biomarkers of response and survival to therapy in OC. Beside their clinical implications, we also discuss important differences between studies that may have limited their use as clinical biomarkers and suggest new approaches. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Contents 1. Introduction .......................................................................................................... 74 2. Molecular events related with poor prognosis in ovarian cancer ................................................................ 74 3. MicroRNAs in ovarian cancer ............................................................................................ 76 3.1. MicroRNAs associated with chemoresistance in ovarian cancer cell lines.................................................... 76 3.2. MicroRNAs associated with chemoresistance in ovarian tumors ........................................................... 79 http://dx.doi.org/10.1016/j.mce.2014.03.006 0303-7207/Ó 2014 Elsevier Ireland Ltd. All rights reserved. Abbreviations: OC, Ovarian cancer; OS, overall survival; miRNAs, microRNAs; HG-SOC, high-grade serous OC; TCGA, The Cancer Genome Atlas; SNPs, single nucleotide polymorphisms; PFS, progression-free survival; FFPE, formalin-fixed paraffin-embedded; EMT, epithelial-to-mesenchymal transition; OSE, ovarian surface epithelium; RNAi, RNA interference; siRNA, small interfering RNA; EVs, extracellular vesicles. ⇑ Corresponding author. Address: Biomedical Research Unit, Vall Hebron Institute of Research, Edifici Collserola, Laboratori 209, Pg. Vall d’Hebron 119-129, 08035 Barcelona, Spain. Tel.: +34 934894052; fax: +34 934894015. E-mail address: jaume.reventos@vhir.org (J. Reventós). 1 Equally contributing. Molecular and Cellular Endocrinology 390 (2014) 73–84 Contents lists available at ScienceDirect Molecular and Cellular Endocrinology journal homepage: www.elsevier.com/locate/mce