Serum Expression Levels of Certain miRNAs in Predicting Diagnosis, Prognosis, and Response to Chemotherapy in Malignant Pleural Mesothelioma

Our plain-English summary of Serum Expression Levels of Certain miRNAs in Predicting Diagnosis, Prognosis, and Response to Chemotherapy in Malignant Pleural Mesothelioma, by M. Metintaş, G. Ak, C. Özbayer, et al (Balkan Medical Journal, 2022).

The study

• Authors: M. Metintaş, G. Ak, C. Özbayer, F. Boğar, S. Metintaş
• Journal: Balkan Medical Journal
• Published: 2022;39(4):246-254
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: miRNAs are involved in tumor pathogenesis and can therefore be determined in the primary tumor, plasma and serum, and body fluids. As in various cancers, their role in the diagnosis, prognosis, and treatment of patients with malignant pleural mesothelioma (MPM) may be important.

Aims: To analyze the predictive value of miR-16-5p, miR-29c-3p, miR-31-5p, miR-125a-5p, miR-320a, miR-484 and miR-532-5p expressions for diagnosis, prognosis and response to treatment in patients with MPM.

Study Design: Prospective case-control study.

Methods: In the first phase of the study, blood samples were collected from 101 MPM patients before chemotherapy and from 24 healthy donors (HDs). In the second phase, the blood samples were collected from 74 MPM patients who had received chemotherapy when the best overall response and disease recurrence were determined. A quantitative real-time polymerase chain reaction was undertaken to detect the miRNA expression levels. The miRNA expression profiles of MPM patients were compared with those of HDs. The associations between the expression levels of miRNAs and prognosis and response to treatment were then evaluated.

Results: All miRNAs, except miR-31-5p, were expressed differently in MPM relative to that in HDs. The expression level of miR-16-5p decreased when compared with that of HDs, and the expression levels of miR-29c-3p, miR-125a-5p, miR-320a, miR-484, and miR-532-5p increased when compared with that of HDs. The sensitivity and specificity values of miR-29c-3p, miR-125a-5p, miR-320a, miR-484, and miR-532-5p for discriminating MPM from HDs were 85.9% and 59.1%, 95.1% and 62.5%, 87.1% and 79.2%, 82.2% and 58.3%, and 69.3% and 82.6%, respectively. After adjusting for the histological subtype, stage, and treatment, the miR-29c-3p, miR-125a-5p, and miR-484 were associated with longer survival. The miRNA expression levels did not change longitudinally for the determination of chemotherapy response and recurrence.

Conclusion: miRNAs may be useful in diagnosing patients with MPM and provides helpful information in determining the prognosis of patients.

In plain English

This prospective case-control study from Turkey measured seven small RNA molecules (microRNAs, or miRNAs) in blood serum. Samples came from 101 untreated patients with malignant pleural mesothelioma (MPM), diagnosed 2015 to 2019, and 24 healthy donors not exposed to asbestos. Six of the seven miRNAs differed between patients and donors; miR-31-5p did not. For telling patients from donors, miR-125a-5p had a sensitivity of 95.1% (interval 88.8 to 98.4) and specificity of 62.5% (40.6 to 81.2); miR-320a had 87.1% (79.0 to 93.0) and 79.2% (57.8 to 92.9). Patients with lower levels of miR-29c-3p, miR-125a-5p and miR-484 survived longer. For miR-125a-5p, median survival was 30.0 months (95% confidence interval 10.8 to 49.2) in the lower-expression group versus 12.0 months (9.6 to 14.4). In 74 patients given platinum-based pemetrexed chemotherapy, miRNA levels did not change with treatment response. They also did not differ between the end of treatment and disease recurrence. The authors concluded that miRNAs may be useful in diagnosing MPM and in judging prognosis. They said further studies are needed on monitoring treatment and recurrence.

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: Prospective case-control study in two phases: (1) diagnosis and survival, comparing patients with healthy donors; (2) follow-up of patients treated with chemotherapy only.
• Who was studied: 101 patients with histologically diagnosed malignant pleural mesothelioma, untreated at sampling, diagnosed May 2015 to April 2019 at the Department of Chest Diseases, Eskişehir Osmangazi University, Turkey. Also 24 healthy donors similar in age and sex and not exposed to asbestos. 74 of the patients, who received only chemotherapy, were assessed for treatment response.
• Exposure: The study measured serum levels of miR-16-5p, miR-29c-3p, miR-31-5p, miR-125a-5p, miR-320a, miR-484 and miR-532-5p. It did not study asbestos exposure and gives no asbestos exposure details for the patients; it states only that the healthy donors had not been exposed to asbestos. Patients in the second phase received platinum-based pemetrexed chemotherapy.
• Main results:
  • Comparing the 101 MPM patients with the 24 healthy donors, all miRNAs except miR-31-5p were expressed differently. miR-16-5p was lower in patients; miR-29c-3p, miR-125a-5p, miR-320a, miR-484 and miR-532-5p were higher.
  • Sensitivity and specificity for telling MPM patients from healthy donors were: miR-29c-3p 85.9% and 59.1%; miR-125a-5p 95.1% and 62.5%; miR-320a 87.1% and 79.2%; miR-484 82.2% and 58.3%; miR-532-5p 69.3% and 82.6%.
  • Table 2 gives intervals for these values. For miR-125a-5p: sensitivity 95.1% (88.8 to 98.4) and specificity 62.5% (40.6 to 81.2). For miR-320a: sensitivity 87.1% (79.0 to 93.0) and specificity 79.2% (57.8 to 92.9).
  • miR-16-5p and miR-31-5p did not significantly distinguish MPM patients from healthy donors.
  • Among the 101 patients, those with lower expression of miR-29c-3p, miR-125a-5p and miR-484 had longer survival.
  • For miR-125a-5p, median survival was 30.0 months (95% CI 10.8 to 49.2) in patients with values above the cut-off of 4.11. It was 12.0 months (95% CI 9.6 to 14.4) in patients at or below the cut-off (p = 0.008).
  • The model was adjusted for cell type, stage and treatment. It gave hazard ratios for the 'Low' group compared with the 'High' group (defined by cut-off values) of 2.299 (95% CI 1.148-4.605) for miR-29c-3p, 5.659 (95% CI 2.067-15.493) for miR-125a-5p and 2.527 (95% CI 1.383-4.619) for miR-484. Receiving no treatment had a hazard ratio of 3.105 (95% CI 1.836-5.251).
  • Of the 74 chemotherapy patients, 22 (29.7%) had progressive disease, 27 (36.5%) stable disease, 24 (32.4%) partial response and 1 (1.4%) complete response. In all response groups, miRNA levels did not differ between before treatment and the best response.
  • miRNA levels at the end of treatment and at disease recurrence were not significantly different.
• The authors' conclusion: The authors concluded that miRNAs may be useful in diagnosing MPM and give helpful information on prognosis, but that further studies are needed for monitoring treatment and detecting recurrence.
• Limitations the authors state:
  • The authors suggested that the lack of an association with miR-31 may be because they did not separate patients by histological subtype.
  • The authors suggested that the lack of a prognostic association with miR-16 may be because they used serum rather than the tissue samples used in earlier studies.
  • The authors noted that treatment-related changes in miRNA levels in the tumor may not be reflected in the serum.

Topics

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

Medical terms in this study, explained in our Lexicon: Prognosis, Chemotherapy, Pleural Mesothelioma, Case-Control Study, Histological Subtype.

Related studies

• Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism — C. De Santi, O. Melaiu, et al. (2017)
• Two Different Serum MiRNA Signatures Correlate with the Clinical Outcome and Histological Subtype in Pleural Malignant Mesothelioma Patients — M. Lamberti, R. Capasso, et al. (2015)
• Secreted and Tissue miRNAs as Diagnosis Biomarkers of Malignant Pleural Mesothelioma — V. Martínez-Rivera, M.C. Negrete-García, et al. (2018)
• Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis — M.B. Kirschner, E. Pulford, 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)
• Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma — M. Matboli, A.E. Shafei, et al. (2019)

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