title: Identification of a chrXq27.3 microRNA cluster associated with early relapse in advanced stage ovarian cancer patients.
abstract: 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.
authors.affiliation: Depts. of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Bagnoli
authors.forename: Loris
authors.initials: L
authors.lastname: De Cecco
authors.forename: Anna
authors.initials: A
authors.lastname: Granata
authors.forename: Roberta
authors.initials: R
authors.lastname: Nicoletti
authors.forename: Edoardo
authors.initials: E
authors.lastname: Marchesi
authors.forename: Paola
authors.initials: P
authors.lastname: Alberti
authors.forename: Barbara
authors.initials: B
authors.lastname: Valeri
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbareschi
authors.forename: Francesco
authors.initials: F
authors.lastname: Raspagliesi
authors.forename: Delia
authors.initials: D
authors.lastname: Mezzanzanica
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D002453:Cell Cycle; D049109:Cell Proliferation; D041321:Chromosomes, Human, X / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D002945:Cisplatin