Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study

Our plain-English summary of Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study, by D.G. Weber, A. Brik, S. Casjens, et al (BMC Research Notes, 2019).

The study

• Authors: D.G. Weber, A. Brik, S. Casjens, K. Burek, M. Lehnert, B. Pesch, D. Taeger, T. Brüning, G. Johnen, MoMar study group
• Journal: BMC Research Notes
• Published: 2019;12(1):77
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case-control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease.

Results: Using prediagnostic plasma samples collected in median 8.9 months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.

In plain English

This study tested whether three blood markers called microRNAs (miR-132-3p, miR-126-3p and miR-103a-3p) could detect malignant mesothelioma before it was diagnosed. The authors used a case-control design nested in the MoMar cohort of 2769 German workers. These workers had formerly been exposed to asbestos and had a confirmed asbestos-related occupational disease. They were recruited from 2008 to 2018 at 26 medical centers. The authors compared blood samples from 17 men who were later diagnosed with mesothelioma against samples from 34 cancer-free men from the same cohort. Controls were matched on gender, age, smoking status and date of blood collection. Case samples were taken a median of 8.9 months before diagnosis. Levels of the three microRNAs did not differ in a statistically significant way between cases and controls. When the test cut-off was set at 98% specificity, each microRNA, and all three combined, detected none of the cases (0% sensitivity). The authors concluded that these microRNAs are not feasible for early detection of mesothelioma. They noted that only 17 cases were available and only three microRNAs were tested.

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: Case-control study nested in a prospective cohort, testing blood biomarkers (microRNAs) in samples collected before diagnosis
• Who was studied: Drawn from the MoMar cohort of 2769 German workers formerly exposed to asbestos, recruited November 2008 to February 2018 at 26 medical centers in Germany. Cases were 17 men later diagnosed with malignant mesothelioma: 10 epithelioid, 2 biphasic, 3 sarcomatoid and 2 of unknown subtype. Controls were 34 cancer-free men from the cohort, two per case, matched on gender, age, smoking status and date of blood collection. Case blood was collected a median of 8.9 months before diagnosis.
• Exposure: Former asbestos exposure in workers with a confirmed asbestos-related occupational disease (asbestosis and/or other nonmalignant pleural diseases caused by asbestos). The article gives no fiber types, products, jobs or doses. The quantities measured were the microRNAs miR-132-3p and miR-126-3p in plasma and miR-103a-3p in the cellular fraction of blood.
• Main results:
  • Median levels in mesothelioma cases versus controls were 0.015 versus 0.016 for miR-132-3p, 2925 versus 1413 for miR-126-3p, and 282 versus 471 for miR-103a-3p. No difference between cases and controls was statistically significant.
  • Area under the ROC curve was 0.542 (95% CI 0.370–0.713) for miR-132-3p, 0.614 (95% CI 0.439–0.789) for miR-126-3p, and 0.603 (95% CI 0.440–0.765) for miR-103a-3p.
  • At a defined specificity of 98%, each microRNA detected none of the 17 cases (0% sensitivity).
  • Using the maximum Youden's Index cut-off, sensitivity and specificity were 71% and 47% for miR-132-3p, 59% and 72% for miR-126-3p, and 82% and 42% for miR-103a-3p.
  • Combining all three microRNAs gave an AUC of 0.605 (95% CI 0.445–0.765). The combination had 0% sensitivity at 98% specificity, and 82% sensitivity with 47% specificity at the maximum Youden's Index.
  • Cases were split by time from blood collection to diagnosis: under 6 months (5 cases), 6 to 12 months (7) and 12 months or more (5). No statistically significant differences were seen between these subgroups for any microRNA.
• The authors' conclusion: The authors concluded that the three microRNAs failed to detect malignant mesothelioma in blood samples taken before diagnosis and are not feasible for early detection of this cancer. They added that the microRNAs might still be useful for prognosis and response to therapy, but this would need appropriate studies.
• Limitations the authors state:
  • The number of incident mesothelioma cases was low: only 17 prediagnostic case samples, diagnosed over about 9 years, were included.
  • Only three microRNAs were analyzed, although other microRNAs have also been suggested as blood-based mesothelioma biomarkers.

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: Malignant Mesothelioma, nested case-control study, Biomarker, Mesothelioma, Prognosis.

Related studies

• Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin - a case-control comparison nested into a prospective cohort of asbestos-exposed workers — G. Johnen, K. Burek, et al. (2018)
• Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers — I. Bononi, M. Comar, et al. (2016)
• Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos — G. Di Mauro, F. Frontini, et al. (2023)
• Circulating microRNA-197-3p as a potential biomarker for asbestos exposure — F. Frontini, I. Bononi, et al. (2021)
• Droplet digital PCR as a novel system for the detection of microRNA‑34b/c methylation in circulating DNA in malignant pleural mesothelioma — H. Sato, J. Soh, et al. (2019)
• 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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