Pb2379: specific alterations in membrane lipid levels as potential biomarkers in dlbcl patients

Topic: 20. Lymphoma Biology & Translational Research Background: Lipids are essential components of cell membranes and are involved in several cellular processes, including the modulation of immune cells such as T cells and natural killer cells that recognize and eliminate cancer cells. Specific lipids have been implicated in the development or progression of lymphoma. Omega-3 and omega-6 fatty acids are both essential fatty acids that the body needs to function properly. The omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have anti-cancer effects by inhibiting the growth of cancer cells in vitro and in animal studies. Arachidonic acid (AA) is an omega-6 polyunsaturated fatty acid involved in the production of several signaling molecules, including eicosanoids, which play a role in inflammation and cancer development. Some studies have suggested that AA levels may be altered in lymphoma and that AA metabolites may serve as potential biomarkers of lymphoma progression and treatment response. However, the relationship between lymphoma and lipids is complex and not fully understood. Aims: To investigate the lipid profile of patients with diffuse large B cell lymphoma (DLBCL) to identify lipidomic signatures that could become alternative targets for therapy. Methods: Membrane phospholipids of mature red blood cells (RBCs) were analysed for fatty acid (FA) profiling (GC-MS). Nutritional status was assessed using a validated food frequency questionnaire. The FA panel included 12 representative fatty acids, the unsaturation index (UI), the peroxidation index (PI) and the enzymatic index of the MUFA and PUFA biosynthetic pathways. Samples obtained from fresh blood of DLBCL patients at diagnosis were compared with healthy controls. Data comparison between the two cohorts was performed using the Kruskal-Wallis test. The significance level was set at p<0.05. All statistical analyses were performed using Past3 and Power BI for graph spider map. Results: 38 patients with aggressive B-cells lymphomas (sex= 13F and 18M Age= range 26-90, BMI range 18-34) and 27 healthy controls were investigated (Sex= 14F and 13M Age= 24-69 range, BMI<25). Lipidomic analysis revealed that several FA species were significantly present in NHL patients, whereas saturated fatty acid (SFA) appeared to be decreased (Figure 1). Looking at specific FA, SFA stearic acid (C18:0) was greatly reduced the lymphoma group, whereas MUFA such as vaccenic acid (C11c18:1) were higher (p=0.0001) than in healthy controls. Interestingly, DLBCL patients showed low levels of omega-3 PUFA, EPA (C20:5) and DHA (C22:6) (p=0.001 and p=0.003) and higher levels of omega-6 PUFA, AA (p=0.0001). In terms of enzymatic activity, NHL patients had lower delta-9-desaturase and delta-6-desaturasi activity according to the strong reduction of stearic acid and linoleic acid, respectively. Finally, we also found a significant difference in UI and PI between the two groups, explaining changes in fluidity, permeability, oxidative stress and damage. Summary/Conclusion: Our results showed that patients with DLBCL have a significantly altered lipid profile compared to healthy donors. Lipidomics has the potential to provide insights into the biology of lymphoma and to identify novel therapeutic targets. Further research is needed to clarify the mechanisms by which lipids may contribute to lymphoma development and progression, and to determine the potential therapeutic implications of targeting lipid metabolism in lymphoma treatment. Acknowledgments: The study was supported in part by AIL Pesaro Onlus. Figure 1.Keywords: Lipid metabolism, DLBCL