弥漫性大B细胞淋巴瘤中mTOR与MRP1的表达及相关性分析

doi:10.3971/j.issn.1000-8578.2015.09.009

弥漫性大B细胞淋巴瘤中mTOR与MRP1的表达及相关性分析

Correlation of mTOR and MRP1 Expression in Patients with Diffuse Large B-cell Lymphoma

摘要

摘要: 目的探讨雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）与多药耐药相关蛋白1（multidrug resistance protein 1, MRP1）在弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）中的表达及其意义。方法选择新疆医科大学附属肿瘤医院2010年1月—2013年6月间确诊的DLBCL患者共109例。采用Western blot法检测p-mTOR蛋白的表达；采用RT-PCR方法检测MRP1的表达，分析p-mTOR蛋白与MRP1 mRNA表达之间的相关性；采用Kaplan-Meier法进行生存分析。结果 p-mTOR及MRP1 mRNA在DLBCL中的表达率分别为58.7%、56.9%；p-mTOR、MRP1 mRNA在GCB型DLBCL与non-GCB型DLBCL中的表达差异具有统计学意义（P<0.01），p-mTOR的表达与MRP1 mRNA的扩增显著相关（P=0.003）。p-mTOR表达阳性组、阴性组患者的3年无进展生存率（progression free survival, PFS）分别为23%、69%，差异具有统计学意义（P=0.003）；MRP1 mRNA扩增阳性组、阴性组患者的3年PFS分别为39%、62%，差异具有统计学意义（P=0.042）。结论 MRP1、mTOR可能参与了DLBCL的发病，MRP1的表达与mTOR信号通路的激活密切相关。

Abstract: Objective To investigate the expression and significance of the mammalian target of rapamycin(mTOR) and multidrug resistance protein 1(MRP1)gene in patients with diffuse large B-cell lymphoma(DLBCL). Methods A total of 109 patients with DLBCL diagnosed from Jan., 2010 to Jun., 2013 were collected from the Affiliated Tumor Hospital, Xinjiang Medical University. The expression of phosphorylated mTOR(p-mTOR) protein and MRP1 mRNA were examined by Western blot and RT-PCR, respectively. Kaplan-Meier method was used for survival analysis. Results The expression of p-mTOR and MRP1 mRNA were 58.7% and 56.9%, respectively(P=0.003). The expression of p-mTOR and MRP1 mRNA in non-germinal center B-cell like(non-GCB) subgroups were significantly higher than those in GCB subgroups(P<0.05). At a median follow-up of 18 months (range 2-52 months), the 3-year progression-free survival (PFS) of patients with positive and negative p-mTOR expression were 23% and 69%(P=0.003). The 3-year PFS of patients with positive and negative MRP1 expression were 39% and 62%(P=0.042). Conclusion Activation of mTOR signaling pathway and MRP1 overexpression play important roles in the development of DLBCL, moreover, MRP1 expression is closely related to mTOR expression.

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