miR-320d与弥漫大B细胞淋巴瘤预后的相关性研究

Correlation between miR-320d and prognosis of diffuse large B-cell lymphoma

目的 探讨miR-320d表达与弥漫大B细胞淋巴瘤（DLBCL）预后的关系.方法 应用EnVision法对山西省肿瘤医院有随访资料的原发于淋巴结的DLBCL 62例石蜡标本进行CD20、CD3、CD10、bcl-6、Mum-1免疫标记检测,根据Hans分类方法将DLBCL分为生发中心B细胞（GCB）型和非生发中心B细胞（non-GCB）型.采用安捷伦16.0高密度芯片对24例DLBCL石蜡标本进行miRNA表达谱筛选,用实时荧光定量PCR方法对62例DLBCL石蜡标本进行miR-320d表达验证.将1 1例淋巴结反应性增生标本作为对照.结果 62例DLBCL中,GCB型22例（35.5％）,non-GCB型40例（64.5％）,GCB型miR-320d表达水平是non-GCB型的3.43倍（P=0.034）.miR-320d在对照组的表达量是DLBCL的5.65倍（P＜ 0.001）.单因素分析示DLBCL中miR-320d低表达组总生存期低于高表达组,差异有统计学意义（P=0.021）.多因素Cox回归模型分析示62例DLBCL中,miR-320d低表达（RR=2.434,95％CI1.148～5.159,P=0.020）为独立于国际预后指数（IPI）的预后不良因素.结论 miR-320d表达下调预示DLBCL预后不良.

Objective To study the expression of miR-320d in diffuse large B cell lymphoma （DLBCL）,and its correlation with prognosis of DLBCL.Methods Sixty cases of DLBCL with the follow-up data were collected from Shanxi Cancer Hospital,and were examined by immunohistochemical EnVision method for CD3,CD10,CD20,bcl-6 and Mum-1.The DLBCL were classified into germinal center B cell-like （GCB） and non-germinal center B cell-like （non-GCB） subtypes according to Hans＆#39; algorithm.Agilent Human miRNA Microarray 16.0 was used to select the miRNAs on 24 cases paraffin-embedded tissue of DLBCL.The expression levels of miR-320d in 62 cases were examined by TaqMan real-time polymerase chain reaction.Eleven cases of reactive hyperplasia of lymph node were selected as control.Results In 62 cases of DLBCL,22 cases （35.5 %） were GCB and 40 cases （64.5 %） were non-GCB subtypes.The expression of miR-320d in GCB was 3.43 times as much as non-GCB subtypes （P =0.034）,and in reactive hyperplasia of lymph node it was 5.65 times as much as in DLBCL （P 〈 0.001）.The low expression groups of miR-320d was significantly correlated with shorter overall survival （P =0.021）.Multivariate Cox proportional hazard regression analysis （including the IPI scores） revealed that the down-regulated miR-320d was the independent predictor in DLBCL （RR =2.434,95 % CI 1.148-5.159,P =0.020）.Conclusions The down-regulated expression of miR-320d might be considered as a distinct subgroup with poor prognosis.