地方性和散发性 Epstein-Barr 病毒阳性和阴性 Burkitt 淋巴瘤的差异蛋白质组学分析。

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

机构信息

Department of Pediatrics, New York Medical College, Valhalla, NY, United States.

Department of Pediatrics, Columbia University, New York, NY, United States.

出版信息

Eur J Cancer. 2015 Jan;51(1):92-100. doi: 10.1016/j.ejca.2014.10.017. Epub 2014 Nov 6.

DOI:10.1016/j.ejca.2014.10.017

PMID:25466511

Abstract

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.

摘要

背景

伯基特淋巴瘤（BL）是全世界儿童中最常见的非霍奇金淋巴瘤，也是撒哈拉以南非洲最常见的儿科恶性肿瘤。地方性（eBL）和散发性（sBL）变体具有不同的流行病学和病毒学特征。尽管基因表达研究已经定义了这两种变体的转录谱，但它们的蛋白质组特征尚未被研究。

方法

我们使用基于差异质谱的同位素标记相对和绝对定量（iTRAQ）分析，比较了代表 EBV+eBL、EBV+sBL 和 EBV+/−健康供体正常 B 细胞的细胞系的蛋白质组表达谱。

结果

总共发现了 144 个具有统计学意义的差异表达蛋白，假发现率（FDR） ⩽0.2。结果显示，特定蛋白的表达过度，这些蛋白与淋巴瘤的发生有明确的联系，如 TUBB2C（FDR 0.05）、UCHL1（FDR 0.05）和 HSP90AB1（FDR 0.1）。根据 BL 的流行病学和病毒学亚型也确定了独特的特征。在 sBL 中，PCNA（FDR 0.05）和 SLC3A2（FDR 0.1）的表达明显过度。在 eBL 中，C1QBP（FDR 0.1）和 ENO1（FDR 0.25）的表达明显过度。比较 EBV+与 EBV-BL 细胞系和 B 细胞，发现 DDX3X（FDR 0.1）的表达明显过度。使用 Western blot 分析对蛋白质进行了验证。