Expression of Non-B Lymphocyte Immunoglobulin G in Bladder Cancer and Its Biological Function
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摘要:
目的 检测非B细胞来源IgG在膀胱癌中的表达, 探讨其对膀胱癌细胞生物学行为的影响。 方法 回顾性分析北京大学人民医院2012年4月至2014年8月89例膀胱癌组织(研究组)及7例正常组织(对照组)免疫组织化学病理切片。研究组平均年龄(68.0±4.3)岁(37~89岁), 其中高级别肿瘤47例, 低级别肿瘤42例; 分别采用蛋白免疫印迹试验(Western bolt)及逆转录-聚合酶链反应(reverse transcription-polymerase chain reaction, RT-PCR)检测膀胱癌细胞系中的非B细胞来源IgG蛋白及mRNA的表达。采用小干扰RNA(small interfering RNA, siRNA)技术敲减IgG的表达, 通过Transwell及Matrigel实验检测膀胱癌细胞系中5637、BIU87细胞的迁移及侵袭能力。 结果 非B细胞来源IgG在膀胱癌中表达阳性, 在正常组织中为阴性, 且IgG的表达与肿瘤分级、大小及是否复发有显著相关性(P均 < 0.05), 而与患者年龄、性别、肿瘤数量无关。Western blot及RT-PCR结果进一步验证非B细胞来源IgG在膀胱癌中表达。敲减IgG后, 通过膀胱癌细胞5637、BIU87的迁移及侵袭至下室的细胞对比, 显示对照组细胞数多于敲减组。 结论 非B细胞来源IgG在膀胱癌中呈现阳性表达并可反映膀胱癌患者的预后情况, 其高表达促进膀胱癌侵袭及转移, 可能成为膀胱癌的治疗靶标。 Abstract:Objective The aim of this study was to investigate the expression of non-B lymphocyte immunoglobulin G(non B-IgG) in bladder cancer and its role in the biological behavior of cancerous cells. Methods The expression of non B-IgG proteins in bladder cancer tissue of 89 cases (study group, aged 37-89 years, median age (68.0±4.3)) and normal bladder tissue of 7 cases(control group) was detected by immunohistochemistry. There were 47 cases of high histological grades, and 42 cases of low grades. The non B-IgG protein and mRNA in bladder cancer cell lines were detected by Western blot and RT-PCR, respectively. After knocking down the expression of IgG in bladder cancer cells, we investigated the migratory and invasive abilities of bladdercancer cells by Transwell and Matrigel assays. Results The rate of positive expression of non B-IgG in bladder cancertissues was higher than that in normal tissues; and the expression of IgG was correlated with tumor size, histological grade and reoccurrence(P < 0.05). However, the expression of non B-IgG had no relation with age, sex, and tumor number(P>0.05). Western blot and RT-PCR results also showed that nonB-IgG was expressed in bladder cancer cells. After knocking down IgG expression, the ability of migration and invasion of bladder cancer cells was inhibited. Conclusions Non B-IgG was over-expressed in bladder cancer tissues, promoting migration and invasion of cancer cells, which indicated that IgG might be a potential therapeutic target of bladder cancer. -
图 4 敲减非B细胞来源IgG后,膀胱癌细胞5637(A)及BIU87(B)的侵袭能力降低
siNC、siRNA:同图 3
表 1 非B细胞来源IgG表达与膀胱癌临床病理学特征的关系
观察项目 例数 IgG阳性表达 P值 - + ++ +++ 年龄(岁) 0.8830 > 60 58 14 22 8 14 ≤60 31 8 11 6 6 性别 0.7724 男 72 17 27 12 16 女 17 5 4 4 4 病理分级 0.0025 高级别移行上皮癌 47 5 18 10 14 低级别移行上皮肿瘤 42 17 13 6 6 肿瘤大小(cm) 0.0015 > 3 29 1 7 7 14 ≤3 50 12 19 8 11 肿瘤数量* 0.2084 < 8 62 18 21 9 14 ≥8 24 4 7 7 6 是否复发* 0.0037 是 33 3 9 7 14 否 43 5 25 8 5 *部分患者临床资料缺失或失访 -
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