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microRNA-16、bcl-2与T淋巴母细胞淋巴瘤/白血病预后的相关性

Significance of microRNA-16 and bcl-2 expression in T lymphoblastic lymphoma/leukemia and its relation with prognosis

摘要目的 探讨microRNA-16(miR-16)表达、bcl-2蛋白与T淋巴母细胞淋巴瘤/白血病(T-LBL/ALL)预后的相关性.方法 应用免疫组织化学EnVision法对山西省肿瘤医院病理科有详细随访资料的70例T-LBL/ALL石蜡标本进行CD1a、CD3、cCD3、CD7、CD10、CD20、CD23、CD34、CD43、CD45 RO、CD99、末端脱氧核苷酸转移酶(TDT)、髓过氧化物酶(MPO)、bcl-2和Ki-67免疫组织化学标记,采用real-time逆转录聚合酶链反应(real-time RT-PCR)方法检测miR-16的表达水平,30例淋巴结反应性增生作为对照.结果 70例T-LBL/ALL中,免疫组织化学结果显示:66例(94.3%)TDT阳性,66例(94.3%) CD99阳性,48例(68.6%) CD3阳性,65例(92.9%) CD7阳性,23例(32.9%)CD10阳性,17例(24.3%)CD34阳性,28例(40.0%)CD1a阳性,36例(51.4%) cCD3阳性,24例(34.3%) bcl-2阳性,26例(37.1%) CD45RO和34例(48.6%) CD43阳性,CD20、CD23和MPO均为阴性.Ki-67≤80%和>80%分别为46例和24例.与淋巴结反应性增生相比较,miR-16在T-LBL/ALL中表达上调,其表达量是淋巴结反应性增生的5.07倍(P =0.001).miR-16基因变化与bcl-2蛋白表达差异有统计学意义(x2=4.147,P=0.042).单因素分析结果显示,miR-16表达水平与预后相关(P=0.041),bcl-2蛋白表达阴性组预后也好于阳性组(P =0.904),其余临床因素及免疫组织化学指标与预后差异均无统计学意义.多因素COX分析结果显示,miR-16低表达组(<中位数)为独立的预后不良因素(P=0.049).结论 T-LBL/ALL中,miR-16的高表达组总体生存率明显高于低表达组,并且是一种独立的预后因素.bcl-2蛋白阴性组总体生存率明显高于阳性组,提示bc1-2蛋白可能与预后相关.miR-16基因低表达组bcl-2蛋白阳性表达率高于高表达组,推测两者之间可能存在负调节关系,在肿瘤发生发展中起作用.

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abstractsObjective To study the expression of miR-16 and bcl-2 in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) and its relationship to prognosis.Methods 70 cases of T-LBL/ALL with follow-up data were studied by using immunohistochemical EnVision method for CD1 a,CD3,cCD3,CD7,CD1O,CD20,CD23,CD34,CD43,CD45RO,CD99,TDT,MPO,bcl-2 and Ki-67.The expression levels of miR-16 were examined by TaqMan real-time polymerase chain reaction (RT-PCR).Thirty cases of reactive lymph node were selected as control.Results Among the 70 cases of T-LBL/ALL,the percentages of tumor cells expression of TDT,CD99,CD3,CD7,CD10,CD34,CD1a,cCD3,bcl-2,CD45RO and CD43 were 94.3% (66/70),94.3% (66/70),68.6% (48/70),92.9% (65/70),32.9% (23/70),24.3% (17/70),40.0% (28/70),51.4% (36/70),34.3% (24/70),37.1% (26/70),and 48.6% (34/70).Separately,while tumor cells expression of MPO,CD20 and CD23 was all negative.A figure of Ki-67 expression > 80% was found in 24 cases and ≤ 80% in 46 cases.The expression of miR-16 was up-regulated in T-LBL/ALL,and it was 5.07 times of the reactive lymph node (P =0.001).The high expression group of miR-16 was significantly correlated with longer over survival (P =0.041).The prognosisof negative bcl-2 group was better than bcl-2 positive one (P =0.904).The relationship of miR-16 and bcl-2 was significant(P =0.042,x2 =4.147).Survival multivariate COX proportional hazard regression analysis revealed that the low expression of miR-16 might be a independent poor prognosis factor (P =0.049).Conclusions While the high expression group of miR-16 has longer OS than that in low expression group.The prognosis of bcl-2 negative was better than bcl-2 positive.miR-16 may be a independent prognosis factor.The relationship of miR-16 and bcl-2 might suggested that gene regulation may be influenced by them.

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中华病理学杂志

中华病理学杂志

2013年42卷11期

748-752页

MEDLINEISTICPKUCSCDCA

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