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. 2021 Nov 15;11(11):1205.
doi: 10.3390/jpm11111205.

Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma

Veronica Filetti  1 , Carla Loreto  1 , Luca Falzone  2 , Claudia Lombardo  3 , Emanuele Cannizzaro  4 , Sergio Castorina  3 , Caterina Ledda  5 , Venerando Rapisarda  5
Affiliations

Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma

Veronica Filetti et al. J Pers Med. .

Abstract

Fluoro-edenite (FE) is an asbestiform fiber identified in Biancavilla (Sicily, Italy). Environmental exposure to FE has been associated with a higher incidence of malignant mesothelioma (MM). The present study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched with healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR (ddPCR) to evaluate differences in the expression levels of the selected miRNAs and their MM diagnostic potential. In addition, further computational analysis has been performed to establish the correlation of these miRNAs with the available online asbestos exposure data and clinic-pathological parameters to verify the potential role of these miRNAs as prognostic tools. ddPCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. Receiver operating characteristic (ROC) analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased overall survival (OS) of MM patients.

Keywords: asbestos; diagnosis; fluoro-edenite; malignant mesothelioma; microRNA; prognosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
MiRNAs expression, reported as number of copies/uL of reaction, in MM cases and healthy controls, through the Mann‒Whitney test, according to: (A) hsa-miR-323a-3p, (B) hsa-miR-101-3p, (C) hsa-miR-20b-5p. Data were represented as the mean with SD.
Figure 2
Figure 2
ROC curves demonstrated the diagnostic value of hsa-miR-323a-3p (100% sensitivity and 100% specificity), hsa-miR-20b-5p (100% sensitivity and 100% specificity), and hsa-miR-101-3p (100% sensitivity and 40% specificity).
Figure 3
Figure 3
Interaction between selected miRNAs and main altered genes in MM via mirDIP gene target analysis. For each miRNA the level of interaction with the 20 genes involved in MM is reported. The intensity of interaction is highlighted with a color scale ranging from yellow (medium interaction) to red (very high interaction).
Figure 4
Figure 4
Normalized miRNAs expression in MM cases exposed and non-exposed to asbestos, through unpaired Student t-test, according to: (A) hsa-miR-323a-3p, (B) hsa-miR-101-3p, (C) hsa-miR-20b-5p. Data are represented as the mean with SD.
Figure 5
Figure 5
Normalized miRNAs expression in different MM stages, through one-way ANOVA test, according to: (A) hsa-miR-323a-3p, (B) hsa-miR-101-3p, (C) hsa-miR-20b-5p. Data are represented as the mean with SD.
Figure 6
Figure 6
Kaplan‒Meier survival curve of hsa-miR-101-3p expression in MM patients according to: (A) OS time; (B) DSS time; (C) PFI time.
See this image and copyright information in PMC

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