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Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European
Elisabetta Casalone1, Giovanni Birolo1, Barbara Pardini2,3
1Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
Abstract:
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.
Insights
Early detection of malignant pleural mesothelioma (MPM) is possible using a panel of three microRNAs (miRNAs) found in serum extracellular vesicles. This discovery offers potential for non-invasive early diagnostic markers for this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis.
- Early detection and intervention are crucial for improving patient outcomes.
- Identifying non-invasive early diagnostic markers for MPM is a significant unmet need.
Purpose of the Study:
- To identify a signature of microRNAs (miRNAs) in serum extracellular vesicles (EVs) as potential early, non-invasive biomarkers for MPM.
- To evaluate the diagnostic capacity of the identified miRNA panel.
Main Methods:
- A case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort.
- Screening of the entire miRNome in serum EVs from preclinical MPM cases and matched controls.
- Analysis of miRNA expression in preclinical samples collected up to five years before MPM diagnosis.
- Validation of the diagnostic model in an independent retrospective cohort.
Main Results:
- Upregulation of miR-11400, miR-148a-3p, and miR-409-3p was observed in preclinical MPM cases compared to controls.
- A 3-miRNA panel demonstrated good classification capacity (AUC = 0.81) in the initial cohort.
- The panel showed enhanced predictive power (AUC = 0.86) in an independent validation cohort.
- The identified EV miRNA signature was detectable up to five years prior to MPM diagnosis.
Conclusions:
- A signature of extracellular vesicle microRNAs can be detected up to five years before malignant pleural mesothelioma diagnosis.
- The identified miRNAs may offer functional insights into the molecular changes preceding MPM development.
- This miRNA panel holds promise as a non-invasive early diagnostic tool for MPM.
