title: The BRCA1/2-directed miRNA signature predicts a good prognosis in ovarian cancer patients with wild-type BRCA1/2.
abstract: Ovarian cancer patients carrying alterations (i.e., germline mutations, somatic mutations, hypermethylations and/or deletions) of BRCA1 or BRCA2 (BRCA1/2) have a better prognosis than BRCA1/2 alteration non-carriers. However, patients with wild-type BRCA1/2 may also have a favorable prognosis as a result of other mechanisms that remain poorly elucidated, such as the deregulation of miRNAs. We therefore sought to identify BRCA1/2-directed miRNA signatures that have prognostic value in ovarian cancer patients with wild-type BRCA1/2 and study how the deregulation of miRNAs impacts the prognosis of patients treated with platinum-based chemotherapy. By analyzing multidimensional datasets of ovarian cancer patients from the TCGA data portal, we identified three miRNAs (hsa-miR-146a, hsa-miR-148a and hsa-miR-545) that target BRCA1/2 and were associated with overall survival and progression-free survival in patients with wild-type BRCA1/2. By analyzing the expression profiles and Gene Ontology functional enrichment, we found that carriers of BRCA1/2 alterations and patients with miRNA deregulation shared a common mechanism, regulation of the DNA repair-related pathways, that affects the prognosis of ovarian cancer patients. Our work highlights that a proportion of patients with wild-type BRCA1/2 ovarian cancers benefit from platinum-based chemotherapy and that the patients who benefit could be predicted from BRCA1/2-directed miRNA signature.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Fuduan
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Haihai
authors.initials: H
authors.lastname: Liang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhou
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.|Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.|Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005838:Genotype; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D010984:Platinum / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; C000594767:MIR545 microRNA, human; C542542:MIRN146 microRNA, human; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D010984:Platinum