Bmi-1基因在不同预后口腔白斑中的表达及其临床意义  

The expression and clinical significance of Bmi-1 gene in oral leukoplakia with different prognosis

作　　者：吴祥冰 王荣艳 龚中坚 朱金晓[2] 朱声荣[3] Wu Xiangbing;Wang Rongyan;Gong Zhongjian;Zhu Jinxiao;Zhu Shengrong(Department of Stomatology,the Affiliated Wuxi People′s Hospital of Nanjing Medical University,Wuxi 214023,China;Department of Stomatology,the Affiliated Wuxi Children′s Hospital of Nanjing Medical University,Wuxi 214023,China;Center of Stomatology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]南京医科大学附属无锡人民医院口腔科,无锡214023 [2]南京医科大学附属无锡儿童医院口腔科,无锡214023 [3]华中科技大学同济医学院附属同济医院口腔医学中心,武汉430030

出　　处：《中华医学杂志》2022年第11期787-794,共8页National Medical Journal of China

基　　金：国家自然科学基金(81502347);江苏省自然科学基金(BK20150119)。

摘　　要：目的:检测Bmi-1基因在口腔白斑细胞和组织中的表达,分析其在口腔白斑恶性转化中的作用及临床意义。方法:免疫组化法检测南京医科大学附属无锡人民医院口腔科和华中科技大学同济医学院附属同济医院口腔医学中心1996至2018年收治的109例口腔白斑患者(其中男51例,女58例,年龄18~74岁)白斑组织样本中Bmi-1表达,分析其表达水平与口腔白斑患者临床病理参数、预后的关联;采用荧光定量逆转录聚合酶链反应(RT-qPCR)和Western蛋白印迹法检测正常口腔黏膜上皮细胞、口腔白斑细胞、口腔鳞癌细胞、口腔白斑组织和配对的邻近正常组织中Bmi-1基因mRNA和蛋白表达水平;在口腔白斑细胞系Leuk-1中沉默Bmi-1基因表达后分析其对Leuk-1细胞增殖、克隆形成和凋亡的影响。结果:Bmi-1在重度和轻度上皮异常增生的口腔白斑组织中的蛋白表达水平差异有统计学意义(6819±994比4713±372,P=0.017);Bmi-1高表达的口腔白斑患者的未癌变生存率为65.5%(36/55),低于Bmi-1低表达者[88.9%(48/54),P=0.003]。Cox回归分析显示Bmi-1的表达水平可作为预测口腔白斑恶性转化的预测指标(HR=2.522,95%CI:1.128~5.640,P=0.024)。Bmi-1在口腔白斑组织中的mRNA表达水平为0.455±0.120,高于其在邻近正常口腔黏膜组织(0.063±0.009,P=0.014);Bmi-1在随访期发生癌变的口腔白斑组织中的mRNA表达水平(1.405±0.397)高于未发生癌变的口腔白斑组织(0.145±0.017,P<0.001);在口腔白斑细胞系Leuk-1中转染Bmi-1-shNC和Bmi-1-shRNA2腺病毒后,二者的克隆形成数(824±40比414±38,P=0.002)和细胞凋亡率(17.7%±2.3%比36.0%±2.0%,P=0.004)差异均有统计学意义。结论:Bmi-1表达上调促进了口腔白斑细胞的恶性生物学行为,Bmi-1表达可作为预测口腔白斑恶性转化的分子标志物。Objective To detect the expression of Bmi-1 in oral leukoplakia(OL)cells and tissues,and analyze its role and clinical significance in the malignant transformation of OL.Methods Immunohistochemistry was used to evaluate Bmi-1 expression in OL samples from 109 patients(51 males,58 females,age range:18-74 years)who were treated in the Department of Stomatology,the Affiliated Wuxi People′s Hospital of Nanjing Medical University and the Center of Stomatology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,between 1996 and 2018.The correlation between Bmi-1 expression level and clinicopathological parameters and prognosis in patients with OL was analyzed.The mRNA and protein expression levels of Bmi-1 gene in normal oral mucosal epithelial cells,OL cells,oral squamous cell carcinoma(OSCC)cells,OL tissues and paired adjacent normal tissues were detected by real-time PCR and Western blotting.The effects of Bmi-1 on the proliferation,colony formation and apoptosis were investigated by silencing expression of Bmi-1 in OL cell lines Leuk-1.Results The protein level of Bmi-1 in OL tissue with severe and mild dysplasia was statistically different(6819±994 vs 4713±372,P=0.017).The OSCC-free survival rate of OL patients with high Bmi-1 expression was 65.5%(36/55),which was lower than that of OL patients with low Bmi-1 expression(88.9%,48/54,P=0.003).Multivariate Cox proportional analysis indicated that Bmi-1 expression was the independent predictor for malignant transformation of OL(HR=2.522,95%CI:1.128-5.640,P=0.024).The mRNA level of Bmi-1 in OL specimens was 0.455±0.120,which was higher than that in paired adjacent normal tissues(0.063±0.009,P=0.014).The Bmi-1 mRNA level in malignant transformed OL specimens was(1.405±0.397),which was higher than that in untransformed OL specimens(0.145±0.017,P<0.001).After transfection of Bmi-1-shNC and Bmi-1-shRNA2 adenovirus into OL cell line Leuk-1,there were significant differences in the number of clone formation(824±40 vs 414±38,P=0.002)

关 键 词：白斑 口腔 BMI-1基因 恶性转化 预后预测 

分 类 号：R781.5[医药卫生—口腔医学]