摘要
目的研究CD44在胶质瘤中的表达和临床意义,以及CD44下调对胶质瘤细胞增殖、侵袭和凋亡的影响。方法检索Oncomine数据库中关于CD44的信息,对其在各类型肿瘤及胶质瘤中的表达情况进行检索。利用R2基因分析可视化平台及TCGA数据库中下载的胶质瘤基因芯片数据集,分析CD44的表达水平与胶质瘤患者预后的关系。通过siRNA抑制CD44的表达,通过CCK-8试验、Transwell小室、流式细胞术检测CD44下调对胶质瘤U251细胞增殖、侵袭和凋亡的影响。结果 Oncomine数据库中共收集了467项不同肿瘤类型的关于CD44的研究结果,对比正常组织,有统计学差异的结果有68项,其中CD44表达增高的有51项,表达降低的有17项。胶质瘤中高表达的有10项,未搜索到低表达的项目,10项研究共包括955例样本。分析R2基因分析可视化平台(包含504例胶质母细胞瘤)及TCGA数据库(包含529例低级别胶质瘤)的基因芯片数据发现,CD44高表达患者预后更差。在胶质母细胞瘤中CD44高、低表达组患者2年生存率分别为13%和25%(P=0.000 1),在低级别胶质瘤中CD44高、低表达组患者5年生存率分别为47%和61%(P=0.001 0)。采用特异性针对CD44基因的siRNA转染U251胶质瘤细胞可显著抑制CD44的表达,与阴性对照组和空白对照组相比,转染组的细胞增殖和侵袭明显受到抑制,且流式细胞学显示转染组对比阴性对照组细胞凋亡率增加,分别为7.10%和4.11%(P<0.05)。结论 CD44在胶质瘤中高表达,可作为胶质瘤预后判断指标及潜在的治疗靶点。
Objective To explore the expression of CD44 and its prognostic role in glioma and investigate the effects of CD44 downregulation on proliferation,invastion and apoptosis of glioma cells.Methods Data about CD44 were retrieved from the Oncomine database and the expression of CD44 in several kinds of tumor was analyzed.We probed the R2：Genomics Analysis and Visualization Platform to study the association of CD44 expression and overall survival（OS）of glioblastoma patients.Kaplan-Meier analysis of the prognosis of low grade glioma patients was performed on the data set downloaded from TCGA database.CD44-siRNA was transfected into U251 glioma cells to inhibit the expression of CD44.The proliferation,invasion and apoptosis of U251 cells was assessed by CCK-8test,Transwell chamber and flow cytometry,respectively.Results Totally,467 studies about expression of CD44 in different types of tumors were identified in the Oncomine database.As compared with the normal tissues,the CD44 expression was statistically significantly different in tumors of 68 studies,upregulated in 51（10in glioma）and downregulated in the other 17（none in glioma）studies.In 10 studies about glioma,CD44 expression was upregulated,and the 10 studies included 955 samples.Data from R2platform（504samples with glioblastoma）and TCGA database（529samples with low grade glioma）showed that patients with high expression of CD44 were correlated with a worse OS.The2-year survival rate was 13% and 25% for the high and low CD44 expression glioblastoma group,respectively（P=0.000 1）.For low grade glioma,the 5-year survival rate was 47%and 61%for the high and low CD44 expression group,respectively（P=0.001 0）.Moreover,the expression level of CD44 was reduced by CD44-siRNA in the U251 cells,the proliferation and invasionof U251 cells was inhibited,flow cytometry showed that the apoptosis rate was 7.10% and 4.11%for the CD44-siRNA transfection group and negative control group（all P〈0.05）.Conclusion CD44 is highly expressed in glioma and its expression is associated with the prognosis of glioma,which may be a promising therapeutic target for glioma.
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2017年第3期241-247,共7页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
国家自然科学基金资助项目(No.81272780)
