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

Oncotarget. 2016 Sep 6;7(36):58606-58637. doi: 10.18632/oncotarget.9686.

Abstract

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.

Keywords: asbestos; biomarker; mesothelioma; microRNA; systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Asbestos / toxicity*
  • Biomarkers, Tumor
  • Computational Biology
  • Epigenesis, Genetic
  • GPI-Linked Proteins / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / chemically induced*
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Mesothelin
  • Mesothelioma / chemically induced*
  • Mesothelioma / diagnosis*
  • Mesothelioma / genetics
  • Mesothelioma, Malignant
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Tissue Array Analysis
  • Tissue Distribution

Substances

  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • MIRN103 microRNA, human
  • MIRN1266 microRNA, human
  • MIRN625 microRNA, human
  • MicroRNAs
  • Asbestos
  • Mesothelin