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ATG5 as biomarker for early detection of malignant mesothelioma
Marco Tomasetti1, Federica Monaco2, Olga Strogovets3
1Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10A, Ancona, 60126, Italy. m.tomasetti@univpm.it.
Objectives:
Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups.
Results:
The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples.
Insights
Autophagy factor ATG5 shows promise for early malignant pleural mesothelioma (MPM) detection in asbestos-exposed individuals up to two years prior to diagnosis. miR-126 and Mesothelin also serve as prognostic biomarkers for MPM.
Area of Science:
- Oncology
- Biomarker Discovery
- Molecular Biology
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis, often linked to asbestos exposure.
- Early diagnosis and effective treatment strategies are crucial for improving patient survival.
- Inflammation and autophagy are implicated in asbestos-induced cellular transformation.
Purpose of the Study:
- To evaluate autophagic factors (ATG5, HMGB1), microRNAs (miR-126, miR-222), and soluble mesothelin-related proteins (Mesothelin) as biomarkers for MPM.
- To assess the performance of these markers in detecting MPM in pre-diagnostic samples from asbestos-exposed individuals.
- To compare biomarker levels across asbestos-exposed individuals (with and without MPM) and healthy subjects.
Main Methods:
- Analysis of ATG5, HMGB1, miR-126, miR-222, and Mesothelin levels in serum samples.
- Investigation of pre-diagnostic samples from asbestos-exposed individuals who later developed MPM.
- Comparative analysis of biomarker expression in MPM patients, asbestos-exposed individuals, and healthy controls.
Main Results:
- ATG5 demonstrated the highest ability to distinguish between asbestos-exposed individuals with and without MPM.
- miR-126 and Mesothelin were identified as significant prognostic biomarkers for MPM.
- ATG5 showed high sensitivity and specificity for detecting MPM in pre-diagnostic samples up to two years before clinical diagnosis.
Conclusions:
- ATG5 is a potential asbestos-related biomarker for early MPM detection.
- Combination of ATG5 with other markers like miR-126 and Mesothelin may enhance diagnostic and prognostic accuracy.
- Further validation in larger, independent cohorts is necessary to confirm the clinical utility of these biomarkers.
