Identification of miRNA-103 in the cellular fraction of human peripheral blood as a potential biomarker for malignant mesothelioma--a pilot study

Our plain-English summary of Identification of miRNA-103 in the cellular fraction of human peripheral blood as a potential biomarker for malignant mesothelioma--a pilot study, by D.G. Weber, G. Johnen, O. Bryk, et al (PloS One, 2012).

The study

• Authors: D.G. Weber, G. Johnen, O. Bryk, K.H. Jöckel, T. Brüning
• Journal: PloS One
• Published: 2012;7(1):e30221
• Cited by: 68 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: To date, no biomarkers with reasonable sensitivity and specificity for the early detection of malignant mesothelioma have been described. The use of microRNAs (miRNAs) as minimally-invasive biomarkers has opened new opportunities for the diagnosis of cancer, primarily because they exhibit tumor-specific expression profiles and have been commonly observed in blood of both cancer patients and healthy controls. The aim of this pilot study was to identify miRNAs in the cellular fraction of human peripheral blood as potential novel biomarkers for the detection of malignant mesothelioma.

Methodology/principal Findings: Using oligonucleotide microarrays for biomarker identification the miRNA levels in the cellular fraction of human peripheral blood of mesothelioma patients and asbestos-exposed controls were analyzed. Using a threefold expression change in combination with a significance level of p<0.05, miR-103 was identified as a potential biomarker for malignant mesothelioma. Quantitative real-time PCR (qRT-PCR) was used for validation of miR-103 in 23 malignant mesothelioma patients, 17 asbestos-exposed controls, and 25 controls from the general population. For discrimination of mesothelioma patients from asbestos-exposed controls a sensitivity of 83% and a specificity of 71% were calculated, and for discrimination of mesothelioma patients from the general population a sensitivity of 78% and a specificity of 76%.

Conclusions/significance: The results of this pilot study show that miR-103 is characterized by a promising sensitivity and specificity and might be a potential minimally-invasive biomarker for the diagnosis of mesothelioma. In addition, our results support the concept of using the cellular fraction of human blood for biomarker discovery. However, for early detection of malignant mesothelioma the feasibility of miR-103 alone or in combination with other biomarkers needs to be analyzed in a prospective study.

In plain English

This pilot study from Germany looked for small RNA molecules called microRNAs in the blood cells (the cellular fraction of blood) as possible markers of malignant mesothelioma. The authors studied 23 untreated patients with pleural mesothelioma, 17 cancer-free people formerly exposed to asbestos, and 25 volunteers from the general population. A screen of 328 microRNAs in patients and asbestos-exposed controls found 49 that differed at least threefold. Only two, miR-20a and miR-103, were significantly lower in patients. In follow-up testing, miR-20a did not differ significantly. miR-103 was significantly lower in patients than in either control group. Using one cut-off, miR-103 correctly identified 83% of patients and 71% of asbestos-exposed controls. Against general-population controls the figures were 78% of patients and 76% of controls, although the discussion gives 84% for the controls. The authors concluded that miR-103 might be a potential minimally-invasive biomarker for diagnosing mesothelioma. They said it needs testing in larger groups and in a prospective study. They also noted that the subgroups used to check for effects of sex and smoking were small; for example, only 11 people were smokers.

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: Pilot biomarker study comparing blood samples from mesothelioma patients and two cancer-free control groups: a microarray screen followed by quantitative real-time PCR testing. Samples were not split into separate training and test sets.
• Who was studied: 23 patients with pleural malignant mesothelioma (mean age 66, range 34 to 84), not treated by surgery, chemotherapy or radiation before sampling. Subtypes were 12 epithelioid, 7 biphasic, 1 sarcomatoid and 3 unknown. Controls were 17 cancer-free people formerly exposed to asbestos (mean age 68) and 25 general-population volunteers (mean age 70), matched to the patients by age, gender and smoking status. The study was approved by the ethics committee of the Ruhr-Universität Bochum, Germany. Collection dates are not given.
• Exposure: The study measured microRNA levels (especially miR-103) in the cellular fraction of peripheral blood. One control group had former asbestos exposure; fiber types, jobs and doses are not described.
• Main results:
  • Of 328 microRNAs screened by microarray, 49 differed more than threefold between mesothelioma patients and asbestos-exposed controls: 34 lower and 15 higher in patients.
  • Only miR-20a (p = 0.0101) and miR-103 (p = 0.0303) showed significant down-regulation in mesothelioma patients in the microarray screen.
  • In PCR testing, the difference in miR-20a between patients and asbestos-exposed controls was not significant.
  • Median miR-103 was 0.612 in patients and 0.635 in asbestos-exposed controls (p = 0.0062). It was 0.630 in general-population controls. The difference was significant for patients vs general-population controls (p less than 0.0001) but not for asbestos-exposed vs general-population controls.
  • Area under the ROC curve for miR-103 was 0.757 (95% CI 0.586 to 0.929) for patients vs asbestos-exposed controls, and 0.871 (95% CI 0.766 to 0.977) for patients vs general-population controls.
  • With a cut-off of 0.621, miR-103 gave 83% sensitivity and 71% specificity for patients vs asbestos-exposed controls. For patients vs general-population controls it gave 78% sensitivity and 76% specificity; the discussion section states 84% specificity for this comparison.
  • No significant differences in miR-103 were found between epithelioid and biphasic mesothelioma, or by gender or smoking status. The association with age was marginal (rs = 0.20, 95% CI minus 0.05 to 0.43).
• The authors' conclusion: The authors concluded that miR-103 showed promising sensitivity and specificity as a new potential biomarker for diagnosing mesothelioma. They said that its use, alone or with other biomarkers, for early detection needs further validation in a prospective study.
• Limitations the authors state:
  • The subgroups used for the confounder comparisons were small (for example, only 11 smokers), so the validity of those subgroup analyses is limited.
  • The study groups were small. miR-103 should be validated in larger groups to get more reliable sensitivity and specificity values.
  • The heat map clustering of samples was imperfect: some cancer-free samples were dispersed among the patient samples.
  • The study was not designed for early detection. The authors state that a prospective study is the most suitable design for that.

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, Mesothelioma, Discovery.

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