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

Abstract

ObjectiveMalignant 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.ResultsUsing 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.Electronic supplementary materialThe online version of this article (10.1186/s13104-019-4113-7) contains supplementary material, which is available to authorized users.

Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies

“…This is exemplified by some promising candidate markers, i.e. miR-103a-3p, miR-132-3p, and 126-3p, that were identified in common casecontrol studies but ultimately failed to detect mesothelioma in prediagnostic samples [45]. Therefore, more marker candidates -preferably of all molecular classesneed to be identified and validated for the completion of a useful and reliable marker panel to detect malignant mesothelioma at early stages.…”

Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation

“…Very recently, Weber et al (94) tried to overcome the limitation related to the cross-sectional design by examining blood samples collected before MPM diagnosis. They analyzed three circulating miRNAs (miR-132-3p, miR-126-3p, and miR-103a-3p), previously reported as differentially expressed among MPM patients and asbestos exposed subjects, using a nested casecontrol approach.…”

“…Taking into account the limitations mentioned above, many authors (74,83,85,94,102) suggested to explore together markers of different origin to overcome the poor sensitivity and specificity of single markers. These studies combine proteins (e.g., mesothelin, fibulin, and osteopontin concentration) and different epigenetic biomarkers, including DNA methylation, expression of miRNA, and also expression of long-noncoding RNAs (lncRNAs), which are non-coding RNAs mostly involved in transcriptional regulation (103).…”

Liquid Biopsy in Malignant Pleural Mesothelioma: State of the Art, Pitfalls, and Perspectives

“…It must be noted that in this study, the authors used different normalizer RNAs for plasma (miR-146) and tissue (U6, RNU44, RNU48). More recently, Weber et al (89) analyzed the levels of miR-126-3p, miR-132-3p, and miR-103a-3p in plasma samples obtained a median of 8.9 months prior to the diagnosis of MPM ( N = 17), and compared them to asbestos-exposed controls ( N = 34). This study indicated 0% sensitivity of these miRNAs considering a specificity of 98%.…”