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

Our plain-English summary of Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma, by M. Matboli, A.E. Shafei, M.A. Ali, et al (Journal of Cellular Biochemistry, 2019).

The study

• Authors: M. Matboli, A.E. Shafei, M.A. Ali, A.I. Gaber, A. Galal, O. Tarek, M. Marei, E. Khairy, N. El-Khazragy, N. Anber, O. Abdel-Rahman
• Journal: Journal of Cellular Biochemistry
• Published: 2019;120(3):3203-3211
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

© 2018 Wiley Periodicals, Inc.

In plain English

This pilot study, from Ain Shams University in Cairo, Egypt, measured four RNA molecules in blood serum: DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3. The authors picked them by searching gene databases, then tested whether they could help diagnose malignant pleural mesothelioma and predict how it would progress. The study tested serum from 100 Egyptian adults recruited from May 2013 to December 2014: 60 newly diagnosed, untreated patients, 20 workers with chronic asbestos exposure but no mesothelioma, and 20 healthy people. The authors reported that patients had higher hsa-miR-2053 and lncRNA-RP1-86D1.3 levels and lower ARSA and DRAM1 levels than the other two groups. However, their own printed median values for hsa-miR-2053 do not match that claim. Each marker was positive in 78.3% to 90% of patients. The four markers combined gave 100% sensitivity, 85% specificity and 94% accuracy. Over a median 18 months of follow-up, patients positive for hsa-miR-2053 had longer progression-free survival (P = 0.05). The authors concluded that their approach identified a biomarker panel for diagnosis and prognosis. They noted the small sample size and called for larger multicenter studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Pilot diagnostic biomarker study: the authors chose four RNAs through bioinformatics (database) analysis, then measured them in serum by quantitative PCR and compared patients with control groups, followed by survival analysis
• Who was studied: 100 Egyptian adults: 60 newly diagnosed, untreated malignant pleural mesothelioma patients, 20 workers with chronic asbestos exposure without mesothelioma, and 20 healthy controls, recruited at Ain Shams University Hospitals, Cairo, from May 2013 to December 2014
• Exposure: Asbestos exposure was used only to define one comparison group (workers with chronic asbestos exposure). The article does not report fiber types, products, jobs or doses. The study's measurements were serum levels of four RNAs (DRAM1 mRNA, ARSA mRNA, hsa-miR-2053, lncRNA-RP1-86D1.3).
• Main results:
  • The authors reported that the mesothelioma group had higher hsa-miR-2053 and lncRNA-RP1-86D1.3 and lower ARSA and DRAM1 mRNA than both the asbestos-exposed group and the healthy controls (P less than 0.001). The printed medians for hsa-miR-2053 (19.3 in patients, 78.3 in healthy controls) do not agree with this for that marker.
  • Sensitivity (share of mesothelioma patients testing positive) was 85% for hsa-miR-2053, 83.3% for lncRNA-RP1-86D1.3, 90% for ARSA mRNA and 78.3% for DRAM1 mRNA
  • The four markers combined gave 100% sensitivity, 85% specificity and 94% accuracy for diagnosing mesothelioma
  • hsa-miR-2053 levels were negatively correlated with ARSA mRNA (r = −0.763, P less than 0.001) and with DRAM1 mRNA (r = −0.842, P less than 0.001)
  • Median follow-up was 18 months. The recurrence rate was 55.7% of the mesothelioma patients.
  • Mesothelioma patients positive for hsa-miR-2053 had longer progression-free survival and lower cumulative hazard (log-rank chi-square 3.89, P = 0.05)
  • The authors state that the prognostic significance of hsa-miR-2053 was confirmed in multivariate analysis. The hazard ratios are given only in a supplementary table not included in the text.
• The authors' conclusion: The authors concluded that their approach identified an RNA-based serum biomarker panel (hsa-miR-2053, lncRNA-RP1-86D1.3, DRAM mRNA and ARSA mRNA) for diagnosing and predicting the course of malignant pleural mesothelioma
• Limitations the authors state:
  • Small sample size, as a pilot study. The authors say larger multicenter studies and laboratory functional studies are needed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker, Asbestos Exposure.

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