机构地区:[1]四川大学华西医院血液科、血液病研究室,成都610041 [2]泸州医学院附属医院血液科,646400
出 处:《中华血液学杂志》2013年第1期36-40,共5页Chinese Journal of Hematology
基 金:四川省科技厅科技支撑计划
摘 要:目的探讨NK/T细胞淋巴瘤(NK/T—celllymphoma,NKTCL)患者外周血游离EB病毒基因BamHI.W、LMP-1、BZLFl及其编码蛋白ZEBRA表达水平在该疾病诊断中的意义,以及与患者临床特征的相关性。方法48例经病理学检查证实的NKTCL患者纳入此研究,选取相同例数的同期其他非霍奇金淋巴瘤(non—Hodgkinlymphoma,NHL)患者(简称NHL组)及健康人(简称正常对照组)作为对照。采用荧光实时定量PCR(FQ—PCR)检测样本血浆中BamHI—W、LMP-1、BZLFl基因拷贝数,ELISA法测定血浆中ZEBRA蛋白水平。应用ROC曲线评价分析各检测指标在NKTCL患者诊断中的价值,并分析其与患者临床特征间的关系。结果48例患者中未治疗者22例,已治疗者26例。NKTCL组患者血浆BamHI—W、LMP-1、BZLFlmRNA表达水平及ZEBRA蛋白表达水平中位数分别为1871拷贝/ml、394拷贝/ml、499拷贝/ml和73.3μg/L,均明显高于NHL组及正常对照组(P〈0.01)。ROC曲线显示LMP-1、BZLFl及ZEBRA的曲线下面积(AUC)均大于0.70,对NKTCL诊断具有一定参考价值,BamHI—W基因表现为较高的敏感性(81.3%),而BZLFl基因则表现为较高的特异性(81.2%)。未治疗患者的LMP-1基因水平明显高于已治疗患者(898拷贝/ml对0拷贝/ml,P=0.050)。患者血浆BamHI-WmRNA表达水平与B症状有一定相关性(P=0.042)。NKTCL组18例未治疗患者中17例(94.4%)3个基因均呈阳性表达,治疗后患者均呈阴性表达。结论联合检测Bam—HI-W、LMP-1、BZLFl基因表达水平能协助诊断NKTCL,并对患者疗效判断可能有一定指导意义。Objective To explore the diagnostic value of serum levels of BamHI-W fragment, latent membrane protein-I (LMP-1), BZLF1 and ZEBRA protein in patients with natural killer( NK)/T-cell lym- phomas (NKTCLs), and to evaluate their relationship with clinical features. Methods A total of 144 cases were analyzed in this study, including 48 NKTCLs patients, 48 other types of non-Hodgkin' s lymphomas (NHL) patients and 48 healthy individuals as controls. Fluorescent quantitative real-time polymerase chain reaction (RQ-PCR) was used to measure the copy number of BamHI-W, LMP-1 and BZLF1 in serum. En- zyme linked immunosorbent assay (ELISA) was applied to measure the serum levels of ZEBRA protein. The relative operating characteristic (ROC) curve was applied in the evaluation of the tested markers in diagnosis of NKTCL patients, and the correlations among the tested markers and clinical feature were analyzed. Results Compared with the controls, NKTCL group showed significantly higher levels of all the tested markers ( P 〈 O. 01 ). The median values of serum BamHI-W, LMP-1 and BZLF1 DNAs level were 1870, 394 and 499 cop- ies/ml, respectively. And the median value of ZEBRA protein level was 73.3 μg/L. Furthermore, the ROC curves analysis revealed that all the area under curve (AUC) of LMP-1, BZLF1 and ZEBRA were more than 0.70, which were probably helpful in the diagnosis of NKTCL. To predict the presence of NKTCL, BamHI-W showed a high sensitivity of 81.3%, while BZLF1 showed a high specificity of 81.2%. Untreated patients seemed to have a significantly higher level of serum LMP1 DNA than that of treated patients ( median value 898 copies/ml vs 0 copies/ml, P = 0. 050 ). Correlation analysis showed that serum BamHI-WDNA level was correlated with the presence of B symptoms. All the three genes expressed in 94.4% of the untreated cases. On the other hand, none of them expressed in treated cases. Conclusions It suggested that combined measurements of BamHI W, LMP1 and BZLF1 DNA level
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