Dataset Information

Insights into the Impact of Age and EBV Infection on Protein Expression and Molecular Characteristics

ABSTRACT: 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 (6 adults, 4 children; 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Burkitt Lymphoma Cell

SUBMITTER: 娱黄

LAB HEAD: huang yu

PROVIDER: PXD068020 | Pride | 2025-12-01

REPOSITORIES: Pride

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

Huang Yu Y Zheng Shuang S Huang Xinyi X Li Shuqi S Zhang Wenhui W Shu Man M Cao Qinghua Q

Discover oncology 20251119 1

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 ( ...[more]

PMID: 41258592

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Project description:Sporadic Burkitt lymphoma (sBL) can be delineated from diffuse large B-cell lymphoma (DLBCL) by a very homogeneous mRNA expression signature. However, it remained unclear whether all three BL variants – sBL, endemic BL (eBL) and immunodeficiency-associated BL (HIV-BL) – represent a uniform biological entity despite their differences in geographical occurrence, association with immunodeficiency and/or incidence of EBV infection. To address this issue, we generated micro RNA (miRNA) profiles from 18 eBL, 31 sBL and 15 HIV-BL cases. In addition, we analyzed the miRNA expression of 86 DLBCL to determine whether miRNA profiles recapitulate the molecular differences between BL and DLBCL evidenced by mRNA profiling. A signature of 38 miRNAs enriched in MYC regulated and NF-kB pathway associated miRNAs was obtained that differentiated BL from DLBCL. The miRNA profiles of sBL and eBL displayed only 6 differentially expressed miRNAs, whereas HIV and EBV infection had no impact on the miRNA profile of BL. In conclusion, miRNA profiling confirms that BL and DLBCL represent distinct lymphoma categories and demonstrates that the three BL variants are representatives of the same biological entity with only marginal miRNA expression differences between eBL and sBL. Archival tumor specimens of 86 diffuse large B-cell lymphoma (DLBCL) and 64 Burkitt lymphoma (BL) patients were obtained. The DLBCL samples have previously been reviewed by a panel of expert hematopathologists and their clinical data were published as part of the RiCOVER-60 trial. The diagnosis of all BL cases was confirmed by histopathology review according to the criteria of the WHO classification. Based on their geographical origin, 31 BL samples were designated as sporadic BL (sBL) and 18 samples as endemic BL (eBL). Fifteen BL cases were diagnosed as immunodeficiency-associated BL (HIV-BL). Of the 18 eBL 14 cases were EBV+ (87.5%), 2 samples were EBV- (12.5%) and for 2 eBL cases the EBV status was unknown. Of the sBL samples 26 were EBV- (86.7%), 4 cases were EBV+ (13.3%) and for 1 case the EBV status was not evaluable. Among the HIV-BL 5 (33.3%) were EBV+, whereas 10 (66.7%) were EBV-.

Project description:The oral cavity is the persistent reservoir for EBV with lifelong infection of resident epithelial and B cells. Infection of these cell types results in distinct EBV gene expression patterns that are regulated by epigenetic modifications involving DNA methylation and chromatin structure. Such regulation of EBV gene expression relies on viral manipulation of the host epigenetic machinery that may inadvertently result in long-lasting, oncogenic host epigenetic reprogramming. To test this hypothesis in the context of EBV infection of epithelial cells, we established a transient infection model to identify the epigenetic consequences after EBV infection of immortalized normal oral keratinocytes and subsequent viral loss. With mounting evidence that EBV can induce epigenetic alterations, we developed a transient infection model where a clonal derivative (designated cl1) from a human telomerase immortalized normal oral keratinocyte (NOK) cell line was infected with a recombinant Akata EBV carrying neomycin resistance and GfP cassette in place of the BXLF1 open reading frame. Infected cells were passaged ten times, and then selection pressure was removed for an additional ten passages to allow for viral loss. Three transiently-infected EBV-negative clones were identified by single cell cloning (designated cl1, cl3, cl4). Uninfected parental clone and cells transfected with PTRUF5 plasmid were passaged alongside the transiently-infected clones. The transcription profiles were analyzed using Affymetrix microarray U133Plus2.0 arrays in duplicate. NOK cells were single cell cloned (designated as cl1) and EBV infected by co-culture with a recombinant Akata EBV strain carrying neomcycin resistance and GFP expression cassette in place of EBV BXLF1. Cells were selected with 350 ug/ml G418. As a selection control, cells were transfected a plasmid carrying a neomycin resistance cassette. Cells were passaged 10 times with G418, followed by removal of selection pressure. After an additional 10 passages, cells were single cell cloned and the presence of EBV was determined by various methods. Three clones were identified as being EBV negative and said to be transiently infected. Uninfected parental and vector transfected cells were passaged in the same manner and also single cell cloned.

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	XA03572LQ_B_1.raw	Raw