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

• Published in: Journal of cellular biochemistry Vol. 120; no. 3; pp. 3203 - 3211
• Main Authors: Matboli, Marwa, Shafei, Ayman E., Ali, Mahmoud A., Gaber, Ahmed I., Galal, Ahmed, Tarek, Osama, Marei, Mohamed, Khairy, Eman, El‐Khazragy, Nashwa, Anber, Nahla, Abdel‐Rahman, Omar
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2019
• Subjects: Arylsulfatase; Asbestos; Autophagy; Bioinformatics; Biomarkers; Cancer; Cerebroside-sulfatase; Cerebroside-Sulfatase - blood; Chronic exposure; Clinical significance; Deoxyribonucleic acid; Diagnostic systems; DNA; DNA damage; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Humans; Linear Models; long noncoding RNA diagnosis; Lung Neoplasms - blood; Male; Membrane Proteins - blood; Mesothelioma; Mesothelioma - blood; Mesothelioma, Malignant; microRNA; MicroRNAs - blood; miRNA; Patients; Phagocytosis; Pleural Neoplasms - blood; Polymerase chain reaction; Real-Time Polymerase Chain Reaction; Regulators; Ribonucleic acid; RNA; RNA, Long Noncoding - blood; Sensitivity analysis; Three axis; microRNA; long noncoding RNA diagnosis; mesothelioma; bioinformatics
• DOI: 10.1002/jcb.27586
• ISSN: 0730-2312

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. This integrated approach has been shown to identify RNA‐based biomarker panel (hsa‐miR‐2053, lncRNA‐RP1‐86D1.3, DRAM messenger RNA [mRNA], and ARSA mRNA) for malignant pleural mesothelioma (MPM) diagnosis and prognosis. These findings extend our knowledge to offer new targets for MPM diagnosis. Besides, hsa‐miR‐2053 expression is a useful prognostic marker for progression‐free survival in MPM.