Circulating extracellular vesicles as a source of multi-ohmic markers of asbestos-related disease and response to treatment in malignant mesothelioma
BASIC DATA OF THE RESEARCH PROJECT
ARRS code: L1-60135
TITLE: Circulating extracellular vesicles as a source of multi-ohmic markers of asbestos-related disease and response to treatment in malignant mesothelioma
PRICE CLASS: D
- PROJECT LEADER: Vita Dolžan, MD, PhD, Prof.
PROJECT LEADER at INSTITUTE OF ONCOLOGY: Viljem Kovač, MD, PhD, Assoc. Prof
- LEADING ORGANISATION: University of Ljubljana, Faculty of Medicine
- PARTICIPATING ORGANIZATION: Institute of Oncology Ljubljana, University Medical Center Ljubljana, University Clinic for Pulmonary Diseases and Allergy Golnik
- DURATION: 1.1.2025 – 31.12.2027
FINANCING: Slovenian Research and Innovation Agency
SHORT SUMMARY:
Occupational as well as environmental exposure to asbestos has been associated with the development of asbestosis, pleural plaques, diffuse pleural thickening, and pleural effusion as well as several types of cancer. One of the most aggressive and fatal cancers associated with asbestos exposure is malignant mesothelioma (MM). The high disease burden and poor prognosis of MM call for the identification of novel and reliable diagnostic, prognostic, and predictive biomarkers for asbestos-related diseases. As extracellular vesicles (EVs) enable both omics-based and targeted analyses of several classes of molecules from their cells of origin carried in the same vesicles and thus protected from degradation, they may provide an enriched source of biomarkers compared to the plasma soluble molecules. Our study aims to identify and validate EV-related non-invasive biomarkers that may predict the risk for developing asbestos-related diseases in occupationally and environmentally asbestos-exposed individuals, and identify biomarkers predictive for disease progression and treatment response in MM patients.
Four clinically and epidemiologically well-characterized cohorts will be included in the exploratory and validation biomarker studies. Cohort 1 will be recruited primarily from subjects occupationally or environmentally exposed to asbestos in the Anhovo region for an exploratory study of multi-omics predictive and diagnostic biomarkers. Cohort 2 will be used for validation and consists of asbestos-exposed cases with diagnosed MM, asbestosis, pleural plaques, and similarly exposed controls with no asbestos diseases who were presented at the State Board for the Recognition of Occupational Asbestos Diseases at the Clinical Institute of Occupational Medicine in Ljubljana. Cohort 3 will be patients treated for MM with first-line immunotherapy at the University Clinic Golnik. Cohort 4 consists of MM patients treated with platinum-based chemotherapy at the Institute of Oncology Ljubljana. Blood samples will be collected from each subject at recruitment and any follow-up and will be stored for isolation and characterization of EVs. Different classes of EVs-enriched and free plasma biomarkers such as miRNAs and proteins will be investigated by omics-based approaches in the exploratory part of the study and most significantly differentially expressed candidates will be validated by targeted approaches. We will also identify and genotype SNPs in genes regulated by differentially expressed miRNAs or proteins.
Due to a large number of potential biomarkers generated with the multi-omics-based approaches, we will use regression-based statistical methods and machine-learning algorithms to create robust models that will integrate clinical, epidemiologic, and biomarker data into a scoring system-based decision algorithms that would enable the translation of composite biomarker-based approach into the screening of the asbestos-exposed individuals for asbestos-related diseases and early diagnosis of MM, and personalized treatment of MM patients.