Proteomic analysis to investigate new therapeutic approaches, biomarkers and pathological mechanism in different diseases

In the present thesis, proteomic and metabolomic analysis were performed to investigate various biological aspects of cancer, viral infection, and metabolic diseases. All the studies were carried out through an untargeted approach using LC-HRMS. The first study focused on cancer vaccine-based immunotherapies. Our findings demonstrated that salmonella infection of sarcoma primary human cells induces the release of immunogenic peptides in the extracellular medium. These peptides showed an HLA-binding ability in silico and a capability to induce an antitumor immune response in vitro. In the second study, the aim was to identify potential MPM biomarkers in serum and pleural effusion. Two candidate biomarkers, GELS for serum and LUM for pleural effusion, were confirmed on a bigger cohort of patients by ELISA. The third study of the thesis focused on cancer patients affected by COVID-19 disease. Our proteomic results showed alterations in the modulation of pathways and proteins associated with immunodeficiency and inflammatory modulation, suggesting that the concomitant presence of cancer condition and viral infection may increase the inflammatory state of patients. The fourth study focused on the investigation of the host circulating exosome’s response to Sars-CoV-2 infection. Our findings showed that circulating exosomes are strongly involved in the processes associated with SARS-CoV-2 infection such as immune response, inflammation and coagulation. In addition, we identified several potential biomarkers that are well correlated with the severity of the disease. The last part of the thesis reports a metaproteomics and metabolomics analysis of the gut microbiota in pediatric obese children subjected to a Mediterranean Diet (MD) intervention. Our results showed that MD induces in pediatric obese patients the modulation of several bacterial species linked to a general improvement of intestinal dysbiosis, inflammation and metabolic syndrome induced by high-fat diets.