BRCA-associated protein 1 (BAP1) and miR-31 combination predicts outcomes in epithelioid malignant pleural mesothelioma.

Content Provider	Europe PMC
Author	Murrone, Albero Cantini, Luca Pecci, Federica Cognigni, Valeria Copparoni, Cecilia Rinaldi, Silvia Fiordoliva, Ilaria Monaco, Federica Rubini, Corrado Barbisan, Francesca Cimadamore, Alessia Giampieri, Riccardo Bianchi, Francesca Tomasetti, Marco Amati, Monica Santarelli, Lory Berardi, Rossana
Copyright Year	2021
Abstract	BackgroundMalignant pleural mesothelioma (MPM) is an aggressive disease, with few available treatment options. Identification of novel prognostic and predictive biomarkers is a priority. In MPM patients, BRCA-associated protein 1 (BAP1) alterations are detected in about 60% of cases and miR-31 seems to be involved in BAP1 regulation at post-transcriptional level. The aim of this study was to evaluate the interaction between BAP1 and miR-31 in MPM and their prognostic role in MPM.MethodsThe expression of BAP1 and miR-31 was analyzed in tissues of 55 MPM patients treated with first-line chemotherapy. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and Log-rank test was used to investigate differences among subgroups. Multivariate Cox regression analysis was used to evaluate independent predictors of survival.ResultsIn the whole cohort, loss of BAP1 was associated with a significant improvement in OS, but not in PFS. Lower miR-31 levels were detected in epithelioid MPM (e-MPM) compared to the non-epithelioid subtypes and resulted associated with BAP1 loss. By looking at the e-MPM subgroup, loss of BAP1 was not able to predict clinical outcome. Conversely, miR-31 levels were significantly associated with PFS (P=0.028), but not with OS (P=0.059). By combining the two biomarkers, e-MPM patients with BAP1 loss/low miR-31 levels showed a better prognosis compared to the ones with BAP1 retained/high miR-31 levels (median OS 22.6 vs. 17.0 months, P=0.017 and median PFS 8.7 vs. 5.1 months, P=0.020). The BAP1 and miR-31 combination was confirmed at multivariate analysis as an independent prognostic factor for e-MPM patients.ConclusionsIn this preliminary study, we found that the prognostic stratification of e-MPM patients may be improved by simultaneously assessing of BAP1 status and miR-31 levels. The two-biomarker score is useful to identify a subgroup of e-MPM tumors characterized by BAP1 retained and high miR-31 levels with worse clinical outcome.
ISSN	20721439
Journal	Journal of Thoracic Disease
Volume Number	13
PubMed Central reference number	PMC8575852
Issue Number	10
PubMed reference number	34795923
e-ISSN	20776624
DOI	10.21037/jtd-21-555
Language	English
Publisher	AME Publishing Company
Publisher Date	2021-10-01
Access Restriction	Open
Rights License	Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0. 2021 Journal of Thoracic Disease. All rights reserved.
Subject Keyword	Malignant mesothelioma BRCA-associated protein 1 (BAP1) miR-31 microRNA prognosis
Content Type	Text
Resource Type	Article
Subject	Pulmonary and Respiratory Medicine