摘要
目的探讨hsa-miR．146b-5p（miR-146b-5p）的表达在弥漫大B细胞淋巴瘤（DLBCL）患者风险评估中的意义。方法选择62例原发于淋巴结的DLBCL患者石蜡样本，应用免疫组织化学EnVision法对所有样本进行CD20、CD3、CDl0、Bcl-6、Mum-1免疫标记，根据Han’s分类方法将DLBCL分为生发中心B细胞型（GCB型）和非生发中心B细胞型（non—GCB型）；应用安捷伦16．0高密度芯片对24例DLBCL患者的石蜡样本进行miRNA表达谱筛选；采用实时定量RT．PCR方法对62例DLBCL患者的石蜡样本进行miR-146b-5p表达水平的验证。以11例淋巴结反应性增生患者标本作为对照。结果62例DLBCL患者中，GCB型22例（35．5％），non—GCB型40例（64．5％），GCB型患者中miR-146b-5p表达水平是non—GCB型患者的3．2倍，差异有统计学意义（P=0．006）。DLBCL患者中miR-146b-5p表达水平是淋巴结反性增生患者的5．4倍，差异有统计学意义（P=0．001）。62例DLBCL患者中，复发者35例（56．5％）。无复发组患者的miR-146b-5p表达水平明显高于复发组，差异有统计学意义（P=0．004）。DLBCL患者中miR-146b-5p高表达组（〉中位值）无复发生存（RFS）率明显高于低表达组（〈中位值），差异有统计学意义（P=0．005），miR-146b-5p的表达与患者总体生存（0s）率没有明显相关性。多因素COX模型分析显示miR-146b-5p低表达（P=0．004）、国际预后指数（IPI）≥3分（P=0．011）为各自独立的预后不良因素。结论DLBCL患者无复发组miR-146b-5p的表达水平明显高于复发组，并且miR-146b-5p高表达组RFS率明显高于低表达组。提示miR-146b-5p可能是DLBCL患者风险评估中的一个新型分子标志物。
Objective To study the expression of miR-146b-5p in diffuse large B cell lymphoma （ DLBCL）, and its relationship with risk assessment. Methods 62 cases of nodal DLBCL with follow-up da- ta were collected from Shanxi Cancer Hospital, and were studied by using immunohistochemical EnVision method for CD3, CD10, CD20, Bel-6 and MUM1. The DLBCLs were classified into germinal center B cell- like （GCB） and non-germinal center B cell-like （non-GCB） subtypes according to Hans＇ algorithm. Agilent Human miRNA Microarray 16.0 was used to select the miRNAs on paraffin-embedded tissues of 24 DLBCL cases. A TaqMan real-time polymerase chain reaction （RT-PCR） method was performed on 62 nodal DLBCL cases to validate the expression levels of miR-146b-5p. 11 cases with reactive lymph node were elected as con- trol. Results In 62 cases of DLBCL, 35.5% of cases were GCB and 64.5% non-GCB subtypes, the ex
pression of miR-146b-5p in GCB was 3.2 times as much as non-GCB subtypes（ P = 0.006）. The expression of miR-146b-5p was up-regulated in DLBCL, and expression level of miR-146b-5p was 5.4 times as much as reactivated lymph node. In 62 cases of DLBCL, 43.5% cases were recurrence-free and 56.5% recurrence. The expression of miR-146b-5p was remarkably up-regulated in recurrence-free group compared with recur- rence group （P = 0. 004）. Moreover, high expression levels of miR-146b-5p in DLBCL were found to be asso- ciated with longer relapse-free survival （ P = 0. 005 ） , but not for overall survival. Multivariate COX proportional hazard regression analysis revealed that low expression of miR-146b-5p （P = 0. 004）and IPI/〉3 （P = 0.011 ） were independent poor prognostic factors in 62 cases of DLBCL. Conclusions The expression of miR-146b-5p was up-regulated in recurrence-free group, and its higher expression levels in DLBCL were associated with improved relapse-free survival. Our results suggested that miR-146b-Sp might be one of markers for risk assessment.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2012年第12期1010-1014,共5页
Chinese Journal of Hematology
基金
山西省自然科学基金（2007011127）
山西省国际合作项目（2011081059）
山西省留学人员重点科研项目（2008-10-5）
关键词
淋巴瘤
大细胞
弥漫型
微RNA
复发
逆转录聚合酶链反应
生物学标记
Lymphoma, large cell, diffuse
MicroRNAs
Recurrence
Reverse transcriptase polymerase chain reaction
Biological markers
