Exploring biological mechanisms and biomarkers through lipidomics

In this Ph.D. thesis lipidomic analysis has been adopted to explore alteration in biological mechanisms and biomarkers in three different case-studies: virus infection, environmental condition, and cancer disease. The first study is focused on the alteration of plasma (161 samples) and cells (peripheral blood mononuclear cells lipids) (21 samples) in patients affected by COVID-19. Our data demonstrated that lipids are involved in the host response, particularly the glycerophospholipids class and fatty acids but also in membrane remodeling and prostaglandins production. Notably, some lipid species resulted suitable to be used as possible biomarkers. The results from the analysis of cells, confirmed the role of lipids in the immune response against SARS-CoV-2 infection. The second part of the research focused on the study of the lipidome alteration caused by different types of gravity in vitro and in vivo. The effects of microgravity was evaluated on human pancreatic ductal adenocarcinoma cell line. It was observed that exposure to microgravity for seven days leads to a morphological alteration, towards the acquisition of stemness profile. The effects of hypergravity was evaluated using a murine model. It was found that this stressfull condition brings to a decreased levels of most of the lipid classes identified. The last part of the research study reports an untargeted and targeted UHPLC-HRMS lipidomics analysis on plasma samples belonging to patients affected by prostate cancer and patients affected by chronic prostate inflammation. Both with elevated levels of prostate specific antigen and for this reason both groups of patients were subjected to biopsy. In this thesis it has been shown how lipidomics can be used to better understand the impairment in biological pathways and mechanisms that occur in the host. Furthermore, it was demonstrated that lipids can be used as a powerful diagnostic tool for some pathologies, avoiding unnecessary and invasive treatments.