Differential proteomic analysis of endemic and sporadic Epstein-Barr virus-positive and negative Burkitt lymphoma

被引:13
作者
El-Mallawany, Nader Kim [1 ]
Day, Nancy [2 ]
Ayello, Janet [1 ]
Van de Ven, Carmella [1 ]
Conlon, Kevin [3 ]
Fermin, Damian [3 ]
Basrur, Venkatesha [3 ]
Elenitoba-Johnson, Kojo [3 ]
Lim, Megan [3 ]
Cairo, Mitchell S. [1 ,4 ,5 ,6 ,7 ]
机构
[1] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA
[2] Columbia Univ, Dept Pediat, New York, NY 10027 USA
[3] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[4] New York Med Coll, Dept Med, Valhalla, NY 10595 USA
[5] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA
[6] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA
[7] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA
关键词
Endemic; Sporadic; Burkitt lymphoma; EBV; Proteomics; CELL LYMPHOMA; EXPRESSION; RESISTANCE; GENE; P53; HEAT-SHOCK-PROTEIN-90; TUMORIGENICITY; GELDANAMYCIN; INHIBITOR; APOPTOSIS;
D O I
10.1016/j.ejca.2014.10.017
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Burkitt lymphoma (BL) is the most common non-Hodgkin lymphoma in children worldwide and the most common paediatric malignancy in sub-Saharan Africa. The endemic (eBL) and sporadic (sBL) variants have distinct epidemiologic and virologic characteristics. Although gene expression studies have defined the transcriptional profiles of both, their proteomic signatures have not been studied. Methods: We compared the proteomic expression profiles using differential mass spectrometry-based isotope tag for relative and absolute quantitation (iTRAQ) analysis of a cell line representing Epstein-Barr virus (EBV)+ eBL, EBV+ and EBV-sBL, and EBV+/-normal B cells from healthy donors. Results: In total, there were 144 differentially expressed proteins with a statistically significant false discovery rate (FDR) of <= 0.2.Results revealed over-expression of specific proteins with well-established links to lymphomagenesis such as TUBB2C (FDR 0.05), UCHL1 (FDR 0.05) and HSP90AB1 (FDR 0.1). Distinct characteristics based upon the epidemiologic and virologic subtypes of BL were also identified. In sBL, PCNA (FDR 0.05) and SLC3A2 (FDR 0.1) were significantly over-expressed. In eBL, C1QBP (FDR 0.1) and ENO1 (FDR 0.25) were significantly over-expressed. Comparison of EBV+ to EBV-BL cell lines and B cells revealed significant over-expression of DDX3X (FDR 0.1). Proteins were validated using Western blot analysis. Conclusion: Our results suggest unique signal transduction pathways associated with EBV infection and epidemiological subtype of BL that may contribute to lymphomagenesis. These proteomic findings provide potential diagnostic, prognostic and therapeutic links to BL. (C) 2014 Elsevier Ltd. All rights reserved.
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收藏
页码:92 / 100
页数:9
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