Association between lymphoma prognosis and aberrant methylation of ID4 and ZO-1 in bone marrow and paraffin-embedded lymphoma tissues of treatment-naive patients
Association between lymphoma prognosis and aberrant methylation of ID4 and ZO-1 in bone marrow and paraffin-embedded lymphoma tissues of treatment-naive patients
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DOI：
10.3892/or.2013.2450
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发表时间：
2013-07-01
期刊：
影响因子：
4.2
通讯作者：
Yu, Li
中科院分区：
文献类型：
--
作者：
Cen, Jian;Shen, Jianliang;Yu, Li
本研究旨在探讨淋巴瘤患者骨髓和石蜡包埋淋巴瘤组织样本中DNA结合因子4 （ID4）抑制剂和紧密连接蛋白1 （ZO-1）基因甲基化异常与淋巴瘤预后的关系。从未接受治疗的淋巴瘤患者获得骨髓活检和石蜡包埋淋巴瘤组织样本，同时从非淋巴瘤患者和慢性胆囊炎和反应性淋巴结患者获得相应的对照样本。采用甲基化特异性PCR （methyl- specific PCR， MSP）分析了ID4和ZO-1启动子区的甲基化状态。对照组的ID4和ZO-1启动子区完全未甲基化，而淋巴瘤患者石蜡包埋淋巴瘤组织中ID4和ZO-1的甲基化率分别为80.4%和84.3%。淋巴瘤患者ID4或ZO-1基因的甲基化阳性率均为92.2%，显著高于对照组（0%）。非霍奇金淋巴瘤患者骨髓和石蜡包埋淋巴瘤组织中ID4和ZO-1基因的甲基化阳性率明显高于霍奇金淋巴瘤患者。与未甲基化的ID4相比，甲基化的ID4淋巴瘤患者的生存率显著降低。ID4和ZO-1基因的甲基化可能是淋巴瘤诊断的特异性分子标记。ID4基因的甲基化可能是淋巴瘤患者预后不良的一个指标。
The aim of the present study was to investigate the association between lymphoma prognosis and aberrant methylation of inhibitor of DNA binding factor 4 (ID4) and tight junction protein 1 (ZO-1) genes in samples isolated from the bone marrow and paraffin-embedded lymphoma tissues of treatment-naive lymphoma patients. The bone marrow biopsy and paraffin-embedded lymphoma tissue samples from treatment-naive lymphoma patients were obtained, along with corresponding control samples from subjects without lymphoma and from lymph nodes of chronic cholecystitis and reactive lymphadenitis patients. Methylation-specific PCR (MSP) reactions were performed to analyze the methylation status on the promoter regions of ID4 and ZO-1. ID4 and ZO-1 promoter regions in the control group were completely unmethylated, whereas the rates of methylation of ID4 and ZO-1 in paraffin-embedded lymphoma tissues of the lymphoma patients were 80.4 and 84.3%, respectively. The methylation positivity rates of both the ID4 or ZO-1 genes in lymphoma patients were 92.2%, which was significantly higher compared to the rates in the control group (0%). The methylation positivity rates of the ID4 and ZO-1 genes in the bone marrow and paraffin-embedded lymphoma tissues of non-Hodgkin lymphoma patients were significantly higher compared to the rates in the Hodgkin lymphoma patients. The survival rate of lymphoma patients with methylated ID4 was significantly lower compared to that of patients with unmethylated ID4. The methylation of the ID4 and ZO-1 genes may be a specific molecular marker for lymphoma diagnosis. The methylation of the ID4 gene may be an indicator of poor prognosis in lymphoma patients.