Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin's lymphoma
Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin's lymphoma
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DOI：
10.1158/1078-0432.ccr-05-2008
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发表时间：
2006-01-15
影响因子：
11.5
通讯作者：
Khanna, R
中科院分区：
文献类型：
--
作者：
Gandhi, MK;Lambley, E;Khanna, R
目的：在约三分之一的霍奇金淋巴瘤(HL)患者的恶性细胞中发现潜伏的EB病毒(EBV)基因组。EBV病毒DNA的检测和定量可能被用作疾病活动性的生物标志物。实验设计：最初，从HL患者的外周血单个核细胞(PBMC)中前瞻性地监测EBV-DNA病毒载量。随后，我们分析了第二组患者血浆中的病毒载量。共检测了58例HL患者(初诊31例，复发6例，长期缓解21例)。结果：所有EBV阳性的HL患者治疗前血浆中均可检测到EBV-DNA。然而，在治疗有效的患者(P=0.0156)、长期缓解期的EB病毒阳性的HL患者(P=0.0011)和所有EB病毒阴性的HL患者(P=0.0238)中均未检出病毒DNA。相反，与EBV阴性或长期缓解期患者相比，EBV阳性的活动期HL患者的PBMC中的EBV-DNA载量与EBV阴性的HL患者或长期缓解的患者没有相关性。结论：游离血浆EBV-DNA具有良好的敏感性和特异性，可作为EBV阳性HL的无创性生物标志物，系列监测可预测疗效。进一步评估游离血浆EBV-DNA作为监测EBV阳性HL患者治疗反应的生物标记物的作用还需要进一步的前瞻性研究。
Purpose: Latent Epstein-Barr virus (EBV) genomes are found in the malignant cells of approximately one-third of Hodgkin's lymphoma (HL) cases. Detection and quantitation of EBV viral DNA could potentially be used as a biomarker of disease activity.Experimental Design: Initially, EBV-DNA viral load was prospectively monitored from peripheral blood mononuclear cells (PBMC) in patients with HL. Subsequently, we analyzed viral load in plasma from a second cohort of patients. A total of 58 patients with HL (31 newly diagnosed, 6 relapsed, and 21 in long-term remission) were tested. Using real-time PCR, 43 PBMC and 52 plasma samples were analyzed.Results: EBV-DNA was detectable in the plasma of all EBV-positive patients with HL prior to therapy. However, viral DNA was undetectable following therapy in responding patients (P = 0.0156), EBV-positive HL patients in long-term remission (P = 0.0011), and in all patients with EBV-negative HL (P = 0.0238). Conversely, there was no association seen for the EBV-DNA load measured from PBMC in patients with active EBV-positive HL patients as compared with EBV-negative HL, or patients in long-term remission. EBV-DNA load in matched plasma/PBMC samples were not correlated.Conclusions: We show that free plasma EBV-DNA has excellent sensitivity and specificity, and can be used as a noninvasive biomarker for EBV-positive HL and that serial monitoring could predict response to therapy. Additional prospective studies are required to further evaluate the use of free plasma EBV-DNA as a biomarker for monitoring response to treatment in patients with EBV-positive HL.