Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma

Our plain-English summary of Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma, by M.B. Kirschner, Y.Y. Cheng, B. Badrian, et al (Journal of Thoracic Oncology, 2012).

The study

• Authors: M.B. Kirschner, Y.Y. Cheng, B. Badrian, S.C. Kao, J. Creaney, J.J. Edelman, N.J. Armstrong, M.P. Vallely, A.W. Musk, B.W. Robinson, B.C. McCaughan, S. Klebe, S.E. Mutsaers, N. van Zandwijk, G. Reid
• Journal: Journal of Thoracic Oncology
• Published: 2012;7(7):1184-91
• Cited by: 99 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: We investigated the ability of cell-free microRNAs (miRNAs) in plasma and serum to serve as a biomarker for malignant mesothelioma (MM).

Methods: Using miRNA microarrays, we profiled plasma samples from MM patients and healthy controls. miRNAs with significantly different abundance between cases and controls were validated in a larger series of MM patients and in an independent series of MM patients using quantitative real-time polymerase chain reaction. Levels of candidate miRNAs were also quantified in MM tumor samples.

Results: We compared cell-free miRNA profiles in plasma from MM patients with healthy controls. Reviewing 90 miRNAs previously reported to be associated with MM, we found that the levels of two miRNAs, miR-29c* and miR-92a, were elevated in plasma samples from MM patients. In addition, we identified 15 novel miRNAs present at significantly higher levels in the plasma of MM patients. Further analysis of candidate miRNAs by real time-quantitative polymerase chain reaction confirmed that one of them, miR-625-3p, was present in significantly higher concentration in plasma/serum from MM patients and was able to discriminate between cases and controls, in both the original and the independent series of patients. MiR-625-3p was also found to be up-regulated in tumor specimens from a group of 18 MM patients, who underwent extrapleural pneumonectomy.

Conclusion: Our data confirm the potential of miR-29c* and miR-92a as candidate tumor markers and reveal that miR-625-3p is a promising novel diagnostic marker for MM.

In plain English

This Australian laboratory study looked for blood microRNAs (small RNA molecules) that might help identify malignant mesothelioma (MM). Using microarrays on plasma from 5 MM patients and 3 healthy controls, the authors found 15 microRNAs at significantly higher levels in the patients. They retested 12 candidates in plasma from 15 MM patients and 14 controls in New South Wales. Only miR-625-3p was significantly raised, 3.8-fold higher in MM patients (p = 0.004). As a test in this group it showed a sensitivity of 73.33% and a specificity of 78.57% (area under the curve 0.824, confidence interval 0.669 to 0.979). In a separate Perth group, serum miR-625-3p was significantly higher in 30 MM patients than in 10 asbestosis patients (p = 0.023; sensitivity 70%, specificity 90%). In tumor samples from 18 MM patients who had extrapleural pneumonectomy, miR-625-3p averaged 4.35-fold higher than in 7 normal pericardial tissue samples. The authors concluded that miR-625-3p is a promising diagnostic marker for MM. They noted that healthy controls were used in the discovery phase and that comparison with people with documented asbestos exposure is still needed.

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: Laboratory biomarker discovery and validation study comparing blood (plasma/serum) and tissue microRNA levels in mesothelioma patients and control subjects
• Who was studied: Microarray discovery: plasma from 5 MM patients and 3 healthy controls. Test cohort (New South Wales): plasma from 15 MM patients and 14 controls (patients with coronary artery disease or healthy subjects). Validation cohort (Perth, Western Australia): serum from 30 MM patients and 10 asbestosis patients. Tissue: 18 archival tumor blocks from MM patients who underwent extrapleural pneumonectomy between 1994 and 2009 in Sydney, and 7 normal pericardial tissue samples from patients without a history of cancer.
• Main results:
  • On microarrays (5 MM patients compared with 3 healthy controls), 15 microRNAs were present at significantly higher levels in the patients.
  • Of 90 microRNAs previously reported to be associated with MM, three (miR-29c*, miR-92a and miR-196b) were significantly higher in patient plasma on the microarray.
  • In the test cohort (15 MM patients compared with 14 controls), plasma miR-625-3p was 3.8-fold higher in MM patients (p = 0.004).
  • In the test cohort, miR-29c* and miR-92a were 1.64-fold and 1.25-fold higher in MM patients, but these differences were not statistically significant (p = 0.098 and p = 0.147).
  • In the test cohort, plasma miR-625-3p distinguished MM patients from controls with an area under the curve of 0.824 (confidence interval 0.669 to 0.979), a sensitivity of 73.33% and a specificity of 78.57%.
  • In the validation cohort, serum miR-625-3p was significantly higher in the 30 MM patients than in the 10 asbestosis patients (p = 0.023), with an area under the curve of 0.793 (confidence interval 0.657 to 0.930), a sensitivity of 70% and a specificity of 90%.
  • In the 18 MM tumor samples, miR-625-3p averaged 4.35-fold higher than in the normal pericardial tissue controls (p = 0.012), with a more than twofold increase in 14 tumor samples.
  • miR-29c* was lower in tumors than in the normal pericardial tissue: it was down-regulated twofold or more in 15 of 18 tumor specimens (average fold change of minus 2.65; p = 0.005).
• The authors' conclusion: The authors concluded that their data confirm the potential of miR-29c* and miR-92a as candidate tumor markers, and that miR-625-3p is a promising novel diagnostic marker for MM.
• Limitations the authors state:
  • Healthy controls were used in the discovery phase, although people with documented asbestos exposure are generally regarded as a better control group.
  • Many people in Australia may be unknowingly exposed to asbestos, and the authors assumed this also applied to their control series.
  • A formal comparison of circulating microRNA levels between MM patients and people with a documented history of asbestos exposure has not yet been done.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Malignant Mesothelioma, Extrapleural Pneumonectomy (EPP), Tumor Marker.

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• ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma — Y.Y. Cheng, M.B. Kirschner, et al. (2013)
• MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2015)
• Identification of miRNA-103 in the cellular fraction of human peripheral blood as a potential biomarker for malignant mesothelioma--a pilot study — D.G. Weber, G. Johnen, et al. (2012)
• miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer — K.M. Foss, C. Sima, et al. (2011)

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