Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis

Luigina Micolucci _, Most Mauluda Akhtar, Fabiola Olivieri, Maria Rita Rippo and Antonio Domenico Procopio

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Oncotarget. 2016; 7:58606-58637. https://doi.org/10.18632/oncotarget.9686

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Luigina Micolucci1,2, Most Mauluda Akhtar1,2, Fabiola Olivieri2,3, Maria Rita Rippo2 and Antonio Domenico Procopio2,3

1 Computational Pathology Unit, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy

2 Laboratory of Experimental Pathology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy

3 Center of Clinical Pathology and Innovative Therapy, Italian National Research Center on Aging (INRCA-IRCCS), Ancona, Italy

Correspondence to:

Luigina Micolucci, email:

Keywords: asbestos, mesothelioma, microRNA, biomarker, systematic review

Received: December 22, 2015 Accepted: April 28, 2016 Published: June 01, 2016


Background: Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is poorly responsive to current treatments. Minimally invasive, specific, and sensitive biomarkers providing early and effective diagnosis in high-risk patients are urgently needed. MicroRNAs (miRNAs, miRs) are endogenous, non-coding, small RNAs with established diagnostic value in cancer and pollution exposure. A systematic review and a qualitative meta-analysis were conducted to identify high-confidence miRNAs that can serve as biomarkers of asbestos exposure and MM.

Methods: The major biomedical databases were systematically searched for miRNA expression signatures related to asbestos exposure and MM. The qualitative meta-analysis applied a novel vote-counting method that takes into account multiple parameters. The most significant miRNAs thus identified were then subjected to functional and bioinformatic analysis to assess their biomarker potential.

Results: A pool of deregulated circulating and tissue miRNAs with biomarker potential for MM was identified and designated as “mesomiRs” (MM-associated miRNAs). Comparison of data from asbestos-exposed and MM subjects found that the most promising candidates for a multimarker signature were circulating miR-126-3p, miR-103a-3p, and miR-625-3p in combination with mesothelin. The most consistently described tissue miRNAs, miR-16-5p, miR-126-3p, miR-143-3p, miR-145-5p, miR-192-5p, miR-193a-3p, miR-200b-3p, miR-203a-3p, and miR-652-3p, were also found to provide a diagnostic signature and should be further investigated as possible therapeutic targets.

Conclusion: The qualitative meta-analysis and functional investigation confirmed the early diagnostic value of two miRNA signatures for MM. Large-scale, standardized validation studies are needed to assess their clinical relevance, so as to move from the workbench to the clinic.

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