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.

Department of Clinical and Molecular Sciences Polytechnic University of Marche Via Tronto 10A Ancona 60126 Italy

Department of Excellence SBSP Biomedical Sciences and Public Health Polytechnic University of Marche Via Tronto 10A Ancona 60126 Italy

Faculty of Science and 1st Faculty of Medicine Charles University Prague 2 128 00 Czech Republic

Mitochondria Apoptosis and Cancer Research Group School of Pharmacy and Medical Science Griffith University Southport Qld 4222 Australia

Molecular Therapy Group Institute of Biotechnology Czech Academy of Sciences Prague West 252 50 Czech Republic

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