A carregar...
Publicação
Proteomics study of malignant and non-malignant pleural effusion and their effect on healthy donor immune cells
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 103.85 KB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
Abstract: Pleural effusion (PE) is a common complication in advanced-stage lung cancer patients but can also occur in other chronic diseases. Identification of cancer cells is the standard approach for the diagnosis of a malignant PE (MPE) with moderate sensitivity. Thus, more sensitive diagnostic tools are urgently needed. In a cohort study, we investigated potential protein diagnostic biomarkers by proteomics analysis to distinguish MPE from other non malignant pathologies. MPE in lung cancer can be distinguished from non-malignant cases by mass spectrometry (MS)-based proteomic analysis. Functional analyses of protein expression in MPE compared with benign PE identified the involvement of metabolic pathways such as glycolysis/gluconeogenesis and extracellular-related pathways. In the following step, we investigated the impact of MPE on immune cells, given that the pleural fluid is in proximity to the tumor microenvironment. Accordingly, the impact of three types of pleural fluid on the viability, cytotoxicity, immunophenotype, and proteomics alteration of peripheral blood immune cells, was examined. Findings indicated that MPE has cytotoxic effects on immune cells and reduced their viability. Proteomics analysis revealed distinct proteome profiles in immune cells after treatment with different types of pleural fluid, highlighting the up-regulation of proteins associated with cell death and vesicle-related pathways. Moreover, the regulatory role of extracellular vesicles derived from lung cancer cells was tested to explore their effects on peripheral immune cells, utilizing proteomics and phosphoproteomics analyses. Exposure of immune cells with tumor-derived extracellular vesicles displayed phosphorylation changes in vitro condition, which were confirmed with immunoblotting analysis. The results are expected to offer insights into the proteome communication of tumor cells and the peripheral immune system in lung cancer, potentially identifying possible targets for the application of intrapleural immunotherapies and diagnostics. In general, this project identified potential protein biomarkers and outlined detailed proteome contexture of different pathological types of the PEs and their impact on the viability and proteomics alteration of immune cells. Moreover, tumor-derived vesicles were demonstrated to influence the immune cells’ phosphoproteome.
Descrição
Palavras-chave
Proteomics study Malignant and non-malignant pleural effusion