骨髓细胞白血病蛋白1长型高表达与恶性多形性腺瘤患者预后的相关性分析

目的研究骨髓细胞白血病蛋白1(myeloid cell leukemia-1,Mcl-1)的两种异构体骨髓细胞白血病蛋白1长型(myeloid cell leukemia-1-long,Mcl-1L)和骨髓细胞白血病蛋白1短型(myeloid cell leukemia-1-short,Mcl-1S)在恶性多形性腺瘤(malignant pleomorphic adenoma,MPA)中的表达,并评估该类患者的预后。方法收集2011年6月至2017年7月开滦总医院、华北理工大学口腔医学院两院口腔颌面外科手术治疗并成功随访的MPA患者56例,良性多形性腺瘤患者52例,通过实时荧光定量PCR(quantitative real-time PCR,qPCR)和蛋白质印迹法检测Mcl-1L和Mcl-1S在MPA中的表达水平,观察两者mRNA及蛋白表达水平,并与良性多形性腺瘤组织对比蛋白水平,分为高表达和低表达组,并经Kaplan Meier曲线分析总体生存时间,Log Rank检验比较组间差异。Cox多因素回归生存分析患者预后相关因素。结果qPCR分析显示与良性多形性腺瘤组织相比,Mcl-1L mRNA在66.1%(37/56)的MPA患者中呈高表达,Mcl-1L在腮腺、舌下腺及其他部位的MPA中mRNA表达水平(分别为2.21±1.07、2.12±1.08、1.83±0.81)均显著高于良性多形性腺瘤组织(1.00±0.19)(P<0.01)。蛋白质印迹法结果显示,Mcl-1L在腮腺、舌下腺及其他部位MPA中的蛋白表达(分别为1.02±0.43、0.71±0.29、0.70±0.30)均显著高于良性多形性腺瘤组织(0.39±0.08)(P<0.01)。Mcl-1L高表达与肿瘤大小(P=0.002)、淋巴结阳性(P=0.045)显著相关。Mcl-1L高、低表达者的Kaplan-Meier生存曲线差异有统计学意义(P=0.017),Mcl-1L高表达患者的生存时间(24.79±9.71)个月]显著短于Mcl-1L低表达的患者(30.59±9.01)个月](P=0.017)。Cox多因素回归生存分析证实Mcl-1L高表达是患者预后不佳的独立危险因素。结论Mcl-1L高表达与MPA患者整体生存时间呈负相关。

Role of overexpression of myeloid cell leukemia-1-long in prognosis of malignant pleomorphic adenoma

Objective To evaluate the clinicopathological significance of the expression of the two myeloid cell leukemia-1 isoforms,myeloid cell leukemia-1-long(Mcl-1L)and myeloid cell leukemia-1-short(Mcl-1S)in malignant pleomorphic adenoma(MPA).Methods A total of 56 patients with MPA treated with surgery,the expression of Mcl-1L and Mcl-1S were detected by quantitative real-time PCR(qPCR)in mRNA level,and by Western blotting in protein level,respectively.The correlation between clinicopathological parameters(gender,age,site,habits,size,node,metastasis,recurrence)was done using the chi-square test.Kaplan-Merier curve was used to analyze the survival in all patients,Log Rank test was performed to observe the difference between groups.Cox′s proportional hazard test was used to identify the factors that were independent predictors of survival.Results qPCR showed overexpression of Mcl-1L in 66.1%MPA patients(37/56),with significant difference in terms of tumor site,significantly higher expression of Mcl-1L in MPA(parotid gland:2.21±1.07,sublingual gland:2.12±1.08,other sites:1.83±0.81)than benign pleomorphic adenoma tissue(1.00±0.19)(P<0.01).Western blotting analysis showed significantly higher expression of Mcl-1L in MPA(parotid gland:1.02±0.43,sublingual gland:0.71±0.29,other sites:0.70±0.30)than benign pleomorphic adenoma tissue(0.39±0.08)(P<0.01).In malignant pleomorphic adenoma patients,high Mcl-1L expression was significantly associated with node positivity(P=0.045),advanced tumor size(P=0.002).Kaplan-Meier survival line analysis indicated a significantly lower survival time in Mcl-1L higher-expression patients(24.79±9.71)than lower-expression patients(30.59±9.01)(P=0.017).Multivariate analysis indicated Mcl-1L to be an independent prognostic factor for MPA(P=0.002).Conclusions The studies suggest that overexpression of Mcl-1L is associated with poor prognosis in MPA.Mcl-1L is an independent prognostic factor in malignant pleomorphic adenoma.