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中国癌症防治杂志

中国癌症防治杂志 ›› 2018, Vol. 10 ›› Issue (2): 113-118.doi: 10.3969/j.issn.1674-5671.2018.02.09

• 临床研究 • 上一篇    下一篇

CD133、CD68和PD-L1在不同病理级别脑胶质瘤组织中的表达及相关性

  

  1. 广西医科大学附属肿瘤医院神经外科；广西医科大学研究生院
  • 出版日期:2018-04-25 发布日期:2018-06-13
  • 通讯作者: 莫立根 E-mail：ligenmo@163.com
  • 基金资助:

    广西自然科学基金资助项目（2015GXNSFAA139160）；广西医疗卫生适宜技术开发与推广应用项目（S2017099）

Expression and significance of CD133，CD68 and PD-L1 in human brain glioma

  • Online:2018-04-25 Published:2018-06-13

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摘要：

目的 探讨人脑胶质瘤组织中胶质瘤干细胞（glioma stem cells，GSCs）标志物CD133、肿瘤相关巨噬细胞（tumor- associated macrophages，TAMs）标志物CD68和负性共刺激分子PD-L1在不同病理级别人脑胶质瘤组织中的表达及其相关性。方法 采用免疫荧光双染法检测不同病理级别脑胶质瘤组织中CD68和PD-L1蛋白的共表达情况；采用实时荧光定量PCR（quantitative real- time fluorescent PCR，qRT-PCR）技术检测30例低级别脑胶质瘤（Ⅰ级和Ⅱ级）组织和30例高级别脑胶质瘤（Ⅲ级和Ⅳ级）组织中CD133、CD68和PD-L1 mRNA的表达，并分析其与临床病理级别之间的相关性。结果 脑胶质瘤组织中PD-L1和CD68共表达在肿瘤相关巨噬细胞上，即大部分PD-L1阳性细胞为肿瘤相关巨噬细胞，高级别组CD68和PD-L1蛋白的共表达明显高于低级别组。在脑胶质瘤组织中，CD133、CD68和PD-L1 mRNA的表达水平均与病理分级呈正相关（r=0.647，P<0.001；r=0.499，P<0.001；r=0.445，P=0.001）；三者在高级别脑胶质瘤组织中的表达均高于低级别脑胶质瘤组织（P＜0.05）； 脑胶质瘤组织中CD133与CD68 mRNA的表达呈正相关（r=0.525，P<0.001），低级别组和高级别组中两者表达亦呈正相关（r=0.518，P=0.005；r=0.500，P=0.007）；脑胶质瘤组织中CD133与PD-L1 mRNA表达呈正相关（r=0.431，P<0.001），低级别组和高级别组两者表达亦呈正相关（r=0.398，P=0.036；r=0.417，P=0.027）。结论 脑胶质瘤组织中PD-L1主要由肿瘤微环境中的TAMs表达；CD133、CD68和PD-L1表达与脑胶质瘤的恶性程度密切相关。

关键词: 脑肿瘤, 胶质瘤干细胞, 肿瘤相关巨噬细胞, PD-L1, 免疫荧光双染, 实时荧光定量PCR

Abstract:

Objective To investigate the expression of glioma stem cell（GSC） marker CD133，the tumor- associated macrophage （TAM） marker CD68 and the negative co- stimulatory molecule PD-L1 in different pathological grades of glioma tissue and their possible correlation. Methods Double immunofluorescence staining was used to detect co- expression of CD68 and PD-L1 protein in glioma tissues of different pathological grades. The expression of CD133，CD68 and PD-L1 genes in 30 cases of low- grade glioma tissue （grade Ⅰ and Ⅱ） and 30 cases of high- grade glioma tissue （grade Ⅲ and Ⅳ） were detected by quantitative real- time fluorescent PCR （qRT-PCR），and correlation with clinical pathological grade was analyzed. Results The majority of PD-L1-positive cells were TAMs，and as the pathological grade of gliomas increased，the co-expression of CD68 and PD-L1 increased. In glioma tissues，pathological grade positively correlated with levels of CD133 （r=0.647，P<0.001），CD68 （r=0.499，P<0.001），and PD-L1（r=0.445，P=0.001）. The expression levels of CD133，CD68 and PD-L1 were significantly higher in high-grade glioma tissue than in low-grade gliomas （P<0.05）. Expression of the CD133 gene positively correlated with that of the CD68 gene across all samples （r=0.525，P<0.001），in low-grade samples （r=0.518，P=0.005），and in high-grade samples（r=0.500，P=0.007）. Expression of the CD133 gene also positively correlated with that of the PD-L1 gene across all samples （r=0.431，P<0.001），in low- grade samples （r=0.398，P=0.036），and in high-grade samples （r=0.417，P=0.027）. Conclusion PD-L1 in glioma tissue is expressed mainly by TAMs in the tumor microenvironment. Expression of CD133，CD68 and PD-L1 relates closely to the tumor degree of malignancy.

Key words:  Brain neoplasms, Glioma stem cells, Tumor-associated macrophages, PD-L1, Double immunofluorescence staining, Quantitative real-time fluorescent PCR