BASIC DATA OF THE RESEARCH PROJECT
- ARRS code: L3-2622
- TITLE: Biological markers of risk for development, progression and treatment response in asbestos related diseases
- PROJECT LEADER: Assoc. Prof. Vita Dolžan
- DURATION: 1.9.2020 - 31.8.2023
- APPLICANT RESEARCH ORGANISATION: THE FACULTY OF MEDICINE,
- PARTICIPATING RESEARCH ORGANISATIONS: INSTITUTE OF ONCOLOGY LJUBLJANA, UNIVERSITY MEDICAL CENTRE LJUBLJANA
- FINANCING: Slovenian Research Agency
BRIEF DESCRIPTION OF THE PROJECT
The long latency period from asbestos exposure to development of asbestos related diseases, the increasing incidence of malignant mesothelioma (MM) and the poor prognosis despite the multimodal treatment calls for the identification of non-invasive molecular predictors for timely diagnosis and for early prediction of the response to treatment. We have designed two clinical studies: a retrospective case-control study that will allow the research of a new group of biological markers of development of asbestos related diseases in individuals that were occupationally exposed to asbestos and a longitudinal follow-up study that will allow us to study the biomarkers of treatment response to malignant mesothelioma (MM) treatment with different chemotherapy regimens. On the gene level, we will assess tag SNPs in immune checkpoint genes as potential independent or composite biomarkers of MM treatment response. We will also investigate, if telomere lengths and genetic factors that may influence their length play a role in the development of MM and its aggressiveness. Serum calretinin is such of particular interest as a potential non-invasive diagnostic or prognostic biomarker. In tumor tissue, calretinin represents one of the most sensitive and specific immunohistochemical biomarkers of MM, and recent reports indicate that its blood levels may increase more than one year before the clinical diagnosis of MM can be made. We will measure calretinin serum levels and investigate genetic and epigenetic factors regulating its expression as potential independent or composite biomarkers of MM development, progression and treatment response. The most innovative aspect of our research, however, is the study of extracellular vesicles (EVs) and their cargo, especially miRNAs. EVs and miRNAs are outstanding tools for studying the molecular processes associated with asbestos-related diseases and can contribute to a better understanding of basic molecular processes and to identification of potential targets enabling new approaches for MM treatment. The risk of developing the asbestos related diseases, as well as the response to treatment, is influenced by many factors whose impact is intertwined, therefor simultaneous impact of different types of biological markers and their interactions with environmental and lifestyle factors must be taken into account in the risk assessment. Taking into account a growing number of potential biomarkers, we will develop multivariate predictive models to integrate the clinical and biomarker data into scoring system based decision algorithms that would enable the translation of biomarker based approaches into clinical practice.
The aims of our study are:
• To identify non-invasive biological markers that may predict the risk for developing asbestos related diseases in asbestos-exposed individuals, as well as to identify biomarkers predictive for disease progression and treatment response in MM patients.
• We hypothesize that by integrating different classes of biomarkers in multivariable predictive models, we would be able to identify novel or more reliable diagnostic, prognostic and predictive biomarkers for MM.