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.

• Keywords
• ATG5, Asbestos exposure, Biomarkers, HMGB1, Malignant pleural mesothelioma, miRNAs,
• MeSH
• Autophagy-Related Protein 5 MeSH
• Asbestos * adverse effects   MeSH
• Early Diagnosis MeSH
• GPI-Linked Proteins adverse effects   MeSH
• Humans MeSH
• Mesothelioma, Malignant * MeSH
• Mesothelin MeSH
• Mesothelioma * diagnosis   MeSH
• MicroRNAs * MeSH
• Biomarkers, Tumor metabolism   MeSH
• Pleural Neoplasms * diagnosis   MeSH
• Lung Neoplasms * diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• ATG5 protein, human MeSH Browser
• Autophagy-Related Protein 5 MeSH
• Asbestos * MeSH
• GPI-Linked Proteins MeSH
• Mesothelin MeSH
• MicroRNAs * MeSH
• Biomarkers, Tumor MeSH

Asbestos exposure leads to epigenetic and epigenomic modifications that, in association with ROS-induced DNA damage, contribute to cancer onset. Few miRNAs epigenetically regulated in MM have been described in literature; miR-126, however, is one of them, and its expression is regulated by epigenetic mechanisms. Asbestos exposure induces early changes in the miRNAs, which are reversibly expressed as protective species, and their inability to reverse reflects the inability of the cells to restore the physiological miRNA levels despite the cessation of carcinogen exposure. Changes in miRNA expression, which results from genetic/epigenetic changes during tumor formation and evolution, can be detected in fluids and used as cancer biomarkers. This article has reviewed the epigenetic mechanisms involved in miRNA expression in MM, focusing on their role as biomarkers of early diagnosis and therapeutic effects.

• Keywords
• early diagnosis, epi-miRNAs, epigenetic biomarkers, malignant mesothelioma, miR-126,
• Publication type
• Journal Article MeSH
• Review MeSH