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


CONCLUSIONS
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.
Computational Pathology Unit, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.|Laboratory of Experimental Pathology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.
Luigina
L
Micolucci
Computational Pathology Unit, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.|Laboratory of Experimental Pathology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.
Most Mauluda
MM
Akhtar
Laboratory of Experimental Pathology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.|Center of Clinical Pathology and Innovative Therapy, Italian National Research Center on Aging (INRCA-IRCCS), Ancona, Italy.
Fabiola
F
Olivieri
Laboratory of Experimental Pathology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.
Maria Rita
MR
Rippo
Laboratory of Experimental Pathology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.|Center of Clinical Pathology and Innovative Therapy, Italian National Research Center on Aging (INRCA-IRCCS), Ancona, Italy.
Antonio Domenico
AD
Procopio
D001194:Asbestos / Q000633:toxicity*; D014408:Biomarkers, Tumor; D019295:Computational Biology; D044127:Epigenesis, Genetic; D058851:GPI-Linked Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000175:diagnosis* / Q000235:genetics; D000090204:Mesothelin; D008654:Mesothelioma / Q000139:chemically induced* / Q000175:diagnosis* / Q000235:genetics; D000086002:Mesothelioma, Malignant; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D046888:Tissue Array Analysis; D014018:Tissue Distribution
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C544749:MIRN103 microRNA, human; C571915:MIRN1266 microRNA, human; C575476:MIRN625 microRNA, human; D035683:MicroRNAs; D001194:Asbestos; D000090204:Mesothelin
asbestos; biomarker; mesothelioma; microRNA; systematic review