Опубликована: Янв. 1, 2024
Pleural mesothelioma (PM) is a rare and aggressive cancer primarily caused by asbestos exposure. Its late diagnosis, due to non-specific symptoms challenges in distinguishing it from other lung diseases, contributes poor patient outcomes. Recent advancements DNA methylation analysis offer new opportunities for improving PM diagnostics. This thesis investigates the potential of as diagnostic tool, presenting novel approaches early accurate detection PM. The first part research identifies biomarkers using EPIC arrays on 11 samples 29 healthy pleura samples, supplemented public datasets lung-related diseases. study reveals 81,968 differentially methylated CpG sites between pleura. Importantly, these profiles enable clear differentiation cancers, addressing critical challenge. To facilitate cost-effective scalable analysis, technology, IMPRESS (Improved Methylation Profiling Restriction Enzymes smMIP Sequencing), was developed. combines methylation-sensitive restriction enzymes single-molecule Molecular Inversion Probes analyze thousands sites. Validation multi-cancer assay targeting 1,791 CpGs across eight types achieved sensitivity 95% specificity 91%. technology demonstrated high non-invasive diagnostics liquid biopsies. In final part, identified PM-specific were integrated into develop an pleural pathologies. A stepwise model sensitivities 88.9% 80.8% specificities 93.3% 100% differentiating non-tumoral conditions metastases, respectively. highlights promise combination platform offers robust, cost-effective, solution detection. These findings provide foundation integrating methylation-based assays clinical practice, potentially treatment, outcomes cancers.
Язык: Английский
