Downregulation of miR-99a/let-7c/miR-125b miRNA cluster predicts clinical outcome in patients with unresected malignant pleural mesothelioma

Anna Truini, Simona Coco, Ernest Nadal, Carlo Genova, Marco Mora, Maria Giovanna Dal Bello, Irene Vanni, Angela Alama, Erika Rijavec, Federica Biello, Giulia Barletta, Domenico Franco Merlo, Alessandro Valentino, Paola Ferro, Gian Luigi Ravetti, Sara Stigliani, Antonella Vigani, Franco Fedeli, David G Beer, Silvio RoncellaFrancesco Grossi

Research output: Contribution to journalArticle

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal overall survival (OS) and to date no molecular markers are available to guide patient management. This study aimed to identify a prognostic miRNA signature in MPM patients who did not undergo tumor resection. Whole miRNA profiling using a microarray platform was performed using biopsies on 27 unresected MPM patients with distinct clinical outcome: 15 patients had short survival (OS<12 months) and 12 patients had long survival (OS>36 months). Three prognostic miRNAs (mir-99a, let-7c, and miR-125b) encoded at the same cluster (21q21) were selected for further validation and tested on publicly available miRNA sequencing data from 72 MPM patients with survival data. A risk model was built based on these 3 miRNAs that was validated by quantitative PCR in an independent set of 30 MPM patients. High-risk patients had shorter median OS (7.6 months) as compared with low-risk patients (median not reached). In the multivariate Cox model, a high-risk score was independently associated with shorter OS (HR=3.14; 95% CI, 1.18-8.34; P=0.022). Our study identified that the downregulation of the miR-99a/let-7/miR-125b miRNA cluster predicts poor outcome in unresected MPM.

Original languageEnglish
Pages (from-to)68627-68640
Number of pages14
JournalOncotarget
Volume8
Issue number40
DOIs
Publication statusPublished - Sep 15 2017

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Keywords

  • Journal Article

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Truini, A., Coco, S., Nadal, E., Genova, C., Mora, M., Dal Bello, M. G., Vanni, I., Alama, A., Rijavec, E., Biello, F., Barletta, G., Merlo, D. F., Valentino, A., Ferro, P., Ravetti, G. L., Stigliani, S., Vigani, A., Fedeli, F., Beer, D. G., ... Grossi, F. (2017). Downregulation of miR-99a/let-7c/miR-125b miRNA cluster predicts clinical outcome in patients with unresected malignant pleural mesothelioma. Oncotarget, 8(40), 68627-68640. https://doi.org/10.18632/oncotarget.19800