Proteomic analysis of Burkitt lymphoma tissues: insights into the impact of age and EBV infection on protein expression and molecular characteristics.

We aim to investigate the molecular heterogeneity of Burkitt lymphoma (BL) by analyzing the impact of age and Epstein-Barr virus (EBV) infection on protein expression in tumor tissues. Using liquid chromatography-mass spectrometry (LC-MS), we performed proteomic analysis on 10 formalin-fixed paraffin-embedded (FFPE) BL tissue samples (5 adults, 5 pediatric; stratified by EBV status) alongside clinical data from 273 BL patients. Clinically, pediatric patients showed higher lactate dehydrogenase (LDH) levels and advanced tumor stages (P < 0.05), while EBV-positive cases exhibited unique metastatic potential. Key findings revealed significant age-related disparities: adult BL patients exhibited 343 differentially expressed proteins (208 up-regulated, 135 down-regulated) compared to pediatric cases, predominantly enriched in energy metabolism (e.g., PFKM, PGM2) and oxidative stress response pathways (e.g., SOD1, IDH1). EBV-positive BL demonstrated distinct molecular signatures, with 176 differentially expressed proteins (93 up-regulated, 83 down-regulated) linked to purine metabolism (e.g., IMPDH2), apoptosis (e.g., MAPK13, BID), autophagy pathway (e.g., ATG3) and cytoskeletal remodeling (e.g., ARHGAP9, SCRIB). Our results provide novel insights into BL pathogenesis, emphasizing the interplay of age and EBV in shaping molecular landscapes. This study underscores the need for multi-omics integration to advance precision therapy strategies for BL subtypes.