Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma

J Cell Biochem. 2019 Mar;120(3):3203-3211. doi: 10.1002/jcb.27586. Epub 2018 Oct 26.

Abstract

Aim and background: Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM.

Methods: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A ( ARSA) gene expression with their epigenetic regulators microRNA ( miR-2053) and long noncoding RNA ( lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed.

Results: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM.

Conclusion: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.

Keywords: bioinformatics; long noncoding RNA diagnosis; mesothelioma; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cerebroside-Sulfatase / blood*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Linear Models
  • Lung Neoplasms / blood*
  • Male
  • Membrane Proteins / blood*
  • Mesothelioma / blood*
  • Mesothelioma, Malignant
  • MicroRNAs / blood*
  • Pleural Neoplasms / blood*
  • RNA, Long Noncoding / blood*
  • Real-Time Polymerase Chain Reaction

Substances

  • DRAM1 protein, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Long Noncoding
  • Cerebroside-Sulfatase