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MicroRNAs as potential biomarkers in malignant pleural mesothelioma

Authors Santoni-Rugiu E, Andersen M, Grauslund M

Received 8 July 2015

Accepted for publication 9 November 2015

Published 23 December 2015 Volume 2016:6 Pages 1—21

DOI https://doi.org/10.2147/CBF.S72199

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Prof. Dr. Sanja Štifter

Peer reviewer comments 2

Editor who approved publication: Dr Hung Khong


Eric Santoni-Rugiu, Morten Andersen, Morten Grauslund

Laboratory of Molecular Pathology, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark


Abstract: Malignant pleural mesothelioma (MPM), a highly lethal cancer strictly related to asbestos exposure, is usually characterized by delayed diagnosis, resistance to current therapies, and dismal prognosis. MPM is difficult to distinguish histologically from nonmalignant reactive mesothelial proliferations (RMPs) as there are no clinically validated immunohistochemical markers yet and the main diagnostic criterion remains deep invasion into the pleura and underlying fat tissue, which is often not appreciable in small pleural biopsies. In this regard, microRNAs (miRNAs), given their size and stability, are particularly attractive biomarkers in formalin-fixed paraffin-embedded tissue specimens for routine pathology. Moreover, circulating miRNAs appear to be promising biomarkers for early detection and monitoring of patients with MPM. Here, we review the studies mostly performed by miRNA arrays and reverse transcription-quantitative polymerase chain reaction in formalin-fixed paraffin-embedded or frozen tissue samples, MPM cell lines, and blood/plasma/serum samples that have highlighted the potential of miRNAs as biomarkers in MPM. Certain studies have pointed to the ability of miRNAs to distinguish the different histological MPM subtypes or separate MPM from lung adenocarcinoma, and other investigations have revealed that miRNAs can aid in differentiating MPM from RMP or have prognostic value in predicting the patient outcome. Mechanistic aspects of the involvement of miRNAs in mesothelioma genesis and possible use of miRNAs as future therapeutic targets in MPM are also emphasized. Finally, limitations of the data currently obtained due to the drawbacks of reverse transcription-quantitative polymerase chain reaction, heterogeneity of MPM tissue samples, and differences in methodological platforms as well as in types of specimens utilized in different studies are discussed. Because of these inherent weaknesses of collected data, further studies assessing the expression and distribution of miRNAs by in situ hybridization in combination with the codetection of their respective targets by immunohistochemistry and further validation of miRNAs’ targets in vitro are warranted to fully reveal the potential clinical utility of miRNAs in MPM.

Keywords: malignant pleural mesothelioma, miRNAs, cancer biomarkers, diagnosis, prognosis, future therapy

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