MiR-21 Is a Novel Diagnostic and Prognostic Circulating Biomarker in Pleural Mesothelioma

Our plain-English summary of MiR-21 Is a Novel Diagnostic and Prognostic Circulating Biomarker in Pleural Mesothelioma, by B. Mosleh, Y. Dong, E. Lang, et al (Diagnostics, 2026).

The study

• Authors: B. Mosleh, Y. Dong, E. Lang, T. Klikovits, K. Sinn, S. Kao, M. Jakopovic, C. Aigner, B. Hegedüs, N. Baldes, S. Bölükbas, B. Dome, M.A. Hoda, V. Laszlo, M. Grusch, K. Schelch
• Journal: Diagnostics
• Published: 2026;16(8)
• Read it: PubMed · Publisher · Free full text

Abstract

Background/Objective: The identification of novel non-invasive diagnostic and prognostic biomarkers is urgently needed in pleural mesothelioma (PM). While soluble mesothelin-related peptides (SMRP) are the most established circulating biomarker, their prognostic value is limited. A wide range of microRNAs (miRs) play diverse roles in regulating gene expression in PM. MiR-21 has been shown to be upregulated in mesothelioma tissue; nevertheless, the diagnostic and prognostic utility of miR-21 in the circulation and its association with survival in PM have not been extensively investigated to date. The objective of the current study was to evaluate miR-21 as a potential blood-based diagnostic and prognostic biomarker in PM. Methods: Plasma samples from PM patients (n = 94) were collected at the time of diagnosis, prior to treatment. Sex- and age-matched healthy individuals (n = 30) served as controls. MiR-21 levels were measured using quantitative RT-PCR and normalized to miR-16, and potential correlations with clinicopathological data were analyzed. Serum SMRP levels were measured in matched patients (n = 84), and a direct comparative analysis of miR-21 and SMRP was conducted. In situ hybridization (ISH) was used to confirm the presence of miR-21 in tumor cells. Results: Plasma miR-21 levels were significantly elevated in PM patients compared to healthy controls (p < 0.001), demonstrating good diagnostic performance (AUC 0.81). The localization of miR-21 in PM cells was confirmed by ISH. High miR-21 levels were associated with significantly shorter median overall survival (12.4 vs. 24.3 months, p < 0.001). Elevated SMRP levels were also associated with reduced survival (12.4 vs. 19.5 months, p = 0.032); however, SMRP did not retain independent prognostic significance in multivariable analysis. In contrast, high-circulating miR-21 was confirmed as an independent predictor for poor survival (HR 3.12, p < 0.001). Conclusions: Our findings highlight that circulating miR-21 is a potential non-invasive biomarker with both diagnostic and independent prognostic value in pleural mesothelioma and outperforms SMRP in multivariable survival analysis. Further research is warranted to validate its role in the biology of this disease and to assess its correlation with outcome and treatment responses.

In plain English

This retrospective multicenter study tested whether miR-21, a small RNA molecule in blood, could help diagnose pleural mesothelioma and predict survival. It used stored samples from 94 patients in Vienna, Zagreb and Sydney, taken at diagnosis before treatment, and from 30 matched healthy controls. Asbestos exposure was not reported. Plasma miR-21, measured relative to plasma miR-16, was higher in patients than in controls (median normalized value 0.40 vs 0.21, p less than 0.001). It distinguished patients from controls with an AUC of 0.809 (95% CI 0.718–0.900), sensitivity 74% (95% CI 64.3–83.3) and specificity 76% (95% CI 58.8–88.2). Tissue staining of 17 tumor specimens showed miR-21 in tumor cells. Median survival was 24.3 months with low and 12.4 months with high miR-21. In a multivariable analysis of 84 patients, high miR-21 remained linked to shorter survival (hazard ratio 3.12, 95% CI 1.78–5.47). The established marker SMRP did not (hazard ratio 1.58, 95% CI 0.93–2.66, p = 0.090). The authors concluded that miR-21 may serve as a potential diagnostic and prognostic marker, but cautioned it is not mesothelioma-specific and needs independent validation.

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: Retrospective multicenter biomarker study using biobank blood samples, with a healthy control group and tissue in situ hybridization
• Who was studied: 94 patients with histologically confirmed pleural mesothelioma (70 from Vienna, Austria; 19 from Zagreb, Croatia; 5 from Sydney, Australia), 74 male, sampled at diagnosis before treatment. 84 of them had serum SMRP measured. 30 sex- and age-matched healthy controls. 17 resected tumor tissue specimens from Vienna. Sampling dates are not stated.
• Exposure: Asbestos exposure was not assessed. The factors studied were plasma miR-21 (measured by quantitative RT-PCR and normalized to miR-16) and serum SMRP. Patients were split into high and low groups at the median miR-21 value (0.401) and the median SMRP value (1.80 nmol/L).
• Main results:
  • Plasma miR-21, measured relative to plasma miR-16, was higher in the 94 patients (median normalized value 0.40, IQR 0.26–0.54) than in the 30 healthy controls (median 0.21, IQR 0.14–0.31), p less than 0.001.
  • For distinguishing patients from healthy controls, miR-21 had an AUC of 0.809 (95% CI 0.718–0.900), with sensitivity 74% (95% CI 64.3–83.3) and specificity 76% (95% CI 58.8–88.2).
  • In situ hybridization detected miR-21 in tumor cells of epithelioid and sarcomatoid tumors. Because of the small sample, no significant correlation between tissue and plasma miR-21 was observed.
  • Plasma miR-21 did not differ significantly by histology, stage, sex or age. It did not correlate significantly with serum SMRP in 84 patients (Pearson r 0.21, p = 0.0631).
  • In all 94 patients, median overall survival was 24.3 months with low miR-21 versus 12.4 months with high miR-21 (HR 1.79, 95% CI 1.14–2.81, p less than 0.001).
  • In epithelioid disease, high miR-21 was associated with worse survival (HR 1.71, 95% CI 1.03–2.84, p = 0.015). The figure legend gives survival of 26.2 months for low versus 15.6 months for high miR-21.
  • In the small non-epithelioid group, survival did not differ significantly between low and high miR-21 (11.8 vs. 3.5 months; HR 1.94, 95% CI 0.69–5.43, p = 0.201).
  • In 84 patients, high SMRP was associated with shorter survival (19.5 vs. 12.4 months for low vs. high; HR 1.55, 95% CI 0.96–2.49, p = 0.032). High SMRP was more common in late-stage disease (p = 0.046).
  • In multivariable analysis of 84 patients, high miR-21 was an independent predictor of survival (HR 3.12, 95% CI 1.78–5.47, p less than 0.001). SMRP was not (HR 1.58, 95% CI 0.93–2.66, p = 0.090). Histology (HR 2.09) and treatment (HR 2.37) were also independent predictors.
• The authors' conclusion: The authors concluded that circulating miR-21 may serve as a potential diagnostic and prognostic, non-invasive biomarker for pleural mesothelioma, and that it outperformed SMRP in multivariable survival analysis. They stated it should not be used as a stand-alone diagnostic test.
• Limitations the authors state:
  • Retrospective design
  • No external validation cohort; prospective validation in independent cohorts is needed
  • Small numbers of patients with non-epithelioid histology and of healthy controls
  • No comparison groups of patients with other relevant diseases
  • Too few tissue samples for quantitative comparison of tissue and blood miR-21
  • miR-21 is not specific to mesothelioma and is raised in other cancers and inflammatory conditions

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Soluble Mesothelin-Related Peptides (SMRP), Mesothelioma, Median Overall Survival.

Related studies

• Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma — B. Ghanim, M.A. Hoda, et al. (2014)
• Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis — B. Mosleh, K. Schelch, et al. (2023)
• Circulating complement component 4d (C4d) correlates with tumor volume, chemotherapeutic response and survival in patients with malignant pleural mesothelioma — T. Klikovits, P. Stockhammer, et al. (2017)
• Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study — L. Brcic, T. Klikovits, et al. (2021)
• Circulating endothelial cell (CEC) as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM) — K. Yoneda, F. Tanaka, et al. (2012)
• The Mesothelioma Systemic Inflammation Score Is Independently Associated with Overall Survival and Predicts Benefit of Multimodality Treatment in Pleural Mesothelioma — B. Mosleh, K. Sinn, et al. (2025)

Browse more research in Diagnostics, or return to medical research.