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. 2023 Apr 20;13(1):6501.
doi: 10.1038/s41598-023-33116-z.

Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos

Giulia Di Mauro #  1 , Francesca Frontini #  1 , Elena Torreggiani #  1 , Maria Rosa Iaquinta  1 , Andrea Caselli  1 , Chiara Mazziotta  1 , Valentina Esposito  1 , Elisa Mazzoni  2 , Roberta Libener  3 , Federica Grosso  4 , Antonio Maconi  3 , Fernanda Martini  1 , Ilaria Bononi #  5 , Mauro Tognon #  6
Affiliations

Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos

Giulia Di Mauro et al. Sci Rep. .

Abstract

The epigenetic role of microRNAs is established at both physiological and pathological levels. Dysregulated miRNAs and their targets appear to be a promising approach for innovative anticancer therapies. In our previous study, circulating miR-197-3p tested dysregulated in workers ex-exposed to asbestos (WEA). Herein, an epigenetic investigation on this circulating miRNA was carried out in sera from malignant pleural mesothelioma (MPM) patients. MiR-197-3p was quantified in MPM (n = 75) sera and comparatively analyzed to WEA (n = 75) and healthy subject (n = 75) sera, using ddPCR and RT-qPCR techniques. Clinicopathological characteristics, occupational, non-occupational information and overall survival (OS) were evaluated in correlation studies. MiR-197-3p levels, analyzed by ddPCR, were significantly higher in MPM than in WEA cohort, with a mean copies/µl of 981.7 and 525.01, respectively. Consistently, RT-qPCR showed higher miR-197-3p levels in sera from MPM with a mean copies/µl of 603.7, compared to WEA with 336.1 copies/µl. OS data were significantly associated with histologic subtype and pleurectomy. Circulating miR-197-3p is proposed as a new potential biomarker for an early diagnosis of the MPM onset. Indeed, miR-197-3p epigenetic investigations along with chest X-ray, computed tomography scan and spirometry could provide relevant information useful to reach an early and effective diagnosis for MPM.

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Conflict of interest statement

The following authors: G.D.M., F.F., E.T., E.M., R.L., F.M., I.B., and M.T. declare that data from this study has been employed, in part, for the Italian patent application number RBI17430-IT. M.R.I., A.C., C.M., F.G., V.E. declare no conflict of interest.

Figures

Figure 1
Figure 1
MiR-197-3p analysis by ddPCR. (A) WEA and HS cohorts: the amount of miR-197-3p is represented as copies/µl of analyzed cDNA (ANOVA ****P < 0.0001; Tukey’s test: MPM vs WEA **P = 0.0036; WEA vs HS ****P = 0.0001); (B) ROC curve for the comparative analysis of miR-197-3p levels in MPM vs. WEA; (C) ROC curve for the comparative analysis of miR-197-3p levels in MPM vs. HS.
Figure 2
Figure 2
MiR-197-3p analysis by RT-qPCR. (A) WEA and HS cohorts: the amount of miR-197-3p is represented as copies/µl of analyzed cDNA (ANOVA P = ns; Tukey's test: MPM vs WEA P = ns; MPM vs HS P = ns; WEA vs HS P = ns). (B) ROC curve for the comparative analysis of miR-197-3p levels in MPM vs. WEA; (C) ROC curve for the comparative analysis of miR-197-3p levels in MPM vs. HS.
Figure 3
Figure 3
MiR-197-3p levels in MPM histotypes. MiR-197-3p expression detected by RT-qPCR (A) and by ddPCR (B). The amount of miR-197-3p is represented as copies/µl of analyzed cDNA.
Figure 4
Figure 4
Overall survival (OS) outcome analysis at 18 months in MPM cohort. (A) Kaplan–Meier (KM) curves for OS in MPM patients related to miR-197-3p expression revealed by RT-qPCR (log-rank P > 0.05) and (B) ddPCR (log-rank P > 0.05). (C) Kaplan–Meier (KM) curves for OS in MPM patients related to histological subtype (log-rank **P = 0.0056). (D) Kaplan–Meier (KM) curves for OS in MPM patients underwent to pleurectomy (log-rank *P = 0.0394).
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