Oncotarget

Research Papers:

Identification of a chrXq27.3 microRNA cluster associated with early relapse in advanced stage ovarian cancer patients

Marina Bagnoli, Loris De Cecco, Anna Granata, Roberta Nicoletti, Edoardo Marchesi, Paola Alberti, Barbara Valeri, Massimo Libra, Mattia Barbareschi, Francesco Raspagliesi, Delia Mezzanzanica and Silvana Canevari _

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Oncotarget. 2011; 2:1265-1278. https://doi.org/10.18632/oncotarget.401

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Abstract

Marina Bagnoli1,§, Loris De Cecco1,§, Anna Granata1, Roberta Nicoletti1, Edoardo Marchesi1, Paola Alberti1, Barbara Valeri2, Massimo Libra3, Mattia Barbareschi4, Francesco Raspagliesi5, Delia Mezzanzanica1,#, Silvana Canevari1,#

1 Depts. of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

2 Department of Pathology and Oncologic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

3 Department of General Pathology, University of Catania, Italy

4 Department of Pathology, Ospedale Santa Chiara, Trento, Italy

5 Department of Oncologic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

§ equally contributing first authors

# equally contributing last authors

Received: December 23, 2011; Accepted: December 30, 2011; Published: December 31, 2011;

Keywords: advanced-stage ovarian cancer, early relapse, microRNA profiling, miR-506, cisplatin, miR-513a-5p, miR-513b

Correspondence:

Silvana Canevari, email:

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.


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