Diagnostic accuracy of circulating miR-126 for malignant pleural mesothelioma: a systematic review and meta-analysis

Our plain-English summary of Diagnostic accuracy of circulating miR-126 for malignant pleural mesothelioma: a systematic review and meta-analysis, by L. Zhang, Q. Zhou, Y.Q. Han, et al (Translational Cancer Research, 2021).

The study

• Authors: L. Zhang, Q. Zhou, Y.Q. Han, P. Li, P.H. Ouyang, M.Y. Wang, Z.D. Hu
• Journal: Translational Cancer Research
• Published: 2021;10(4):1856-1862
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Circulating microRNAs are novel diagnostic markers for various types of cancer. Several studies have investigated the diagnostic accuracy of circulating miR-126 for malignant pleural mesothelioma (MPM), but the results varied. Therefore, we performed a systematic review and meta-analysis to investigate the diagnostic value of circulating miR-126 for MPM.

Methods: The PubMed database was searched to identify potentially eligible studies published before October 2020. The studies investigating the diagnostic value of circulating miR-126 for MPM were included in a systematic review and meta-analysis. A bivariate model was used to pool eligible studies' sensitivity and specificity. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to assess eligible studies' quality.

Results: Four studies with 156 MPM patients and 459 controls were included in this systematic review and meta-analysis. The pooled diagnostic sensitivity and specificity of circulating miR-126 for MPM were 0.71 and 0.69, respectively. A high risk of bias was observed in the domains of patient selection, index test, and flow and timing.

Conclusions: Circulating miR-126 has limited value for diagnosing MPM. Considering that the available studies have a high risk of bias, further rigorous studies are needed to assess the diagnostic value of circulating miR-126 for MPM.

2021 Translational Cancer Research. All rights reserved.

In plain English

This article was a systematic review and meta-analysis that pooled earlier studies; it did not test new patients. The authors searched the PubMed database for studies published before October 1, 2020 on whether blood levels of a molecule called circulating miR-126 could identify malignant pleural mesothelioma. Four studies, three from Italy and one from Germany, qualified. Together they covered 156 people with malignant pleural mesothelioma and 459 comparison subjects, who included asbestos-exposed subjects, healthy controls and people with non-small cell lung cancer. Pooled across the four studies, the test correctly flagged 0.71 of mesothelioma patients (sensitivity, 95% CI 0.63 to 0.77) and correctly cleared 0.69 of comparison subjects (specificity, 95% CI 0.56 to 0.80). An overall accuracy measure, the summary area under the curve, was 0.74 (95% CI 0.70 to 0.77). Results varied widely between studies. The authors rated the included studies' quality as low, with a high risk of bias. The authors concluded that circulating miR-126 had low diagnostic accuracy, could not replace existing markers, and needed more rigorous study. They named the small sample size as the main limitation.

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: Systematic review and meta-analysis of diagnostic accuracy studies, pooled with a bivariate model; study quality assessed with QUADAS-2
• Who was studied: Four published studies (three from Italy, one from Germany) found by a PubMed search of studies published before October 1, 2020. Total of 615 subjects: 156 with malignant pleural mesothelioma (MPM) and 459 non-MPM subjects. The non-MPM subjects were asbestos-exposed subjects, healthy controls and patients with non-small cell lung cancer.
• Exposure: This is not an asbestos exposure study. What was evaluated was a blood test, circulating miR-126, as a diagnostic marker for malignant pleural mesothelioma. Asbestos-exposed subjects appeared only as comparison groups in some included studies, and no fiber types were named.
• Main results:
  • Pooled across the four studies, circulating miR-126 had a sensitivity of 0.71 (95% CI 0.63 to 0.77) and a specificity of 0.69 (95% CI 0.56 to 0.80) for malignant pleural mesothelioma.
  • The pooled diagnostic odds ratio was 5.35 (95% CI 2.72 to 10.52).
  • The area under the summary receiver operating characteristic (sROC) curve for miR-126 was 0.74 (95% CI 0.70 to 0.77).
  • In the individual studies, sensitivity ranged from 0.59 to 0.76 and specificity ranged from 0.54 to 0.86.
  • Results differed greatly between the studies (I-squared 76%, 95% CI 48% to 100%). The authors attributed all of this heterogeneity (100%) as likely due to the threshold effect.
  • The authors rated the overall quality of the included studies as low. All four studies had a high risk of bias in patient selection because subjects were not enrolled consecutively. All four had a high risk of bias in the index test because the cut-off was defined from the data. Three studies had a high risk of bias in flow and timing because not all subjects received the same reference test.
  • The authors compared their pooled results with figures from earlier meta-analyses of other markers (SMRP, osteopontin, fibulin-3). The specificity and AUC of miR-126 were the lowest of these markers.
• The authors' conclusion: The authors concluded that the diagnostic accuracy of circulating miR-126 for malignant pleural mesothelioma was low and that it could not replace traditional markers. Because some of the included studies had design flaws, they said further rigorous studies are needed.
• Limitations the authors state:
  • The main limitation was the small sample size, which produced wide 95% confidence intervals for sensitivity, specificity and AUC.
  • Because only four studies were included, the authors could not run subgroup analysis or meta-regression to find the source of the heterogeneity. Sensitivity analysis and publication bias analysis were also not performed.
  • The included studies did not prespecify the miR-126 cut-off and none used separate training and validation cohorts. The authors said this may overestimate accuracy, especially in small studies.
  • Not all included studies followed the STARD reporting guideline, so some design details were unclear and risk of bias could not be assessed accurately.
  • The review protocol was not registered or published in advance.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Systematic Review, Meta-Analysis.

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