Circulating microRNAs as biomarkers for risk assessment and prognostic stratification of pleural mesothelioma

Introduction: Pleural mesothelioma (PM) is an aggressive neoplasm associated with asbestos exposure. Clinical management of PM poses major challenges due to the lack of reliable markers for early diagnosis and prognostic stratification. Here we evaluated circulating microRNAs (miRNAs) as minimally invasive biomarkers for PM detection and risk assessment. Methods: Plasma samples were collected from 32 asbestos-exposed (AsbEX) individuals and 56 PM patients, including epithelioid (N = 45) and non-epithelioid (N = 11) subtypes. An initial discovery cohort (9 AsbEX and 9 PM) was screened for 92 miRNAs using quantitative RT-PCR. Candidate miRNAs were validated in the full cohort. Results: Ratios calculated from the plasma levels of miR-24-3p, miR-146a-5p, miR-191-5p, miR-200a-3p, miR-222-3p, miR-223-3p, and miR-1260a robustly differentiated PM patients from asbestos-exposed controls with high accuracy and sensitivity. Furthermore, ratios of circulating miR-146a-5p, miR-200a-3p, miR-222-3p and miR-191-5p enabled stratification of epithelioid PM in high- and low-risk prognostic groups. Conclusion: Circulating miRNA signatures represent promising non-invasive biomarkers for early PM detection and prognostic stratification, particularly in epithelioid cases. Incorporation of these biomarkers into clinical workflows could pave the way for more personalized treatment strategies and optimize patient selection for surgery.