BICD货物接头蛋白1基因作为胶质瘤级别进展分子标志物的研究

BICD cargo adaptor 1 gene as a biomarker of grade progress of glioma

目的检测BICD货物接头蛋白1(BICD1)基因在中国人群各级别胶质瘤样本中的表达水平,并探讨其在低级别胶质瘤向高级别胶质瘤进展过程中的潜在作用。方法从中国脑胶质瘤基因组图谱(CGGA)的全转录组表达谱芯片数据库和全转录组测序数据库中收集BICD1的mRNA表达数据,结合胶质瘤的世界卫生组织(WHO)级别、分子亚型、患者无进展生存期和总生存期及经典分子标志物的表达与突变数据,分析BICD1表达与胶质瘤的级别进展及恶性程度的相关性。收集WHOⅡ、Ⅲ和Ⅳ级胶质瘤组织各10例,提取RNA并反转录为c DNA进行实时荧光定量PCR(qPCR),分析各级别胶质瘤样本中BICD1在转录水平上的表达差异。结果 CGGA全转录组表达谱芯片和全转录组测序数据库中提取的表达数据显示,BICD1的表达水平随着胶质瘤的级别升高而升高(WHOⅢ及Ⅳ级vs WHOⅡ级:t=7.901,P<0.01)。qPCR结果显示较高级别的胶质瘤组织中BICD1的表达水平更高(WHOⅢ级vs WHOⅡ级:t=3.514,P<0.01;WHOⅣ级vsⅢ级:t=2.128,P=0.037 6)。BICD1高表达与胶质瘤患者更短的无进展生存期和总生存期均有关(P均<0.01)。BICD1在前神经元型、神经元型、经典型和间质型胶质瘤样本中的表达水平不同(F=21.8,P<0.01),其中间质型胶质瘤样本中BICD1表达水平最高,前神经元型胶质瘤样本中表达水平最低。BICD1的表达水平与异柠檬酸脱氢酶1(IDH1)突变、染色体1p19q联合缺失、人第10号染色体缺失的磷酸酶和张力蛋白同源基因(PTEN)突变等指示胶质瘤恶性程度的经典分子标志物相关,其中IDH1突变胶质瘤样本中BICD1的表达水平低于野生型样本(t=7.769,P<0.01)。结论 BICD1可能是指示低级别胶质瘤发生级别进展和恶性进展的潜在分子标志物。

Objective To determine the expression level of BICD cargo adaptor 1(BICD1)gene in different grades of glioma in Chinese population,and to explore its potential role in progress of low-grade glioma to high-grade.Methods The BICD1 mRNA expression data were derived from whole transcriptome expression profile array database and whole transcriptome sequencing database of Chinese Glioma Genome Atlas(CGGA).The information of World Health Organization(WHO)grade,molecular subtype,progression-free survival,overall survival,and expression levels and mutation status of typical molecular biomarkers were also collected from the database.The correlation of BICD1 expression with progression and malignancy grade was analyzed.Ten samples of glioma of WHOⅡ,ⅢandⅣgrade were collected,and the extracted RNA was reverse transcribed into cDNA.Then real-time quantitative PCR(qPCR)was performed to analyze BICD1 expression levels in each grade.Results Expression levels derived from whole transcriptome expression profile array database of CGGA and whole transcriptome sequencing database of CGGA showed that BICD1 expression level was significantly increased with WHO grade of glioma(WHOⅢandⅣgrade vs WHOⅡgrade:t=7.901,P<0.01).qPCR analysis showed that BICD1 expression level was significantly higher in the glioma of high-grade versus the glioma of low-grade(WHOⅢgrade vs WHOⅡgrade:t=3.514,P<0.01;WHOⅣgrade vsⅢgrade:t=2.128,P=0.037 6).High expression of BICD1 was significantly correlated with shorter progression-free survival and overall survival of the glioma patients(both P<0.01).The BICD1 expression levels were significantly different between the proneural,neural,classical and mesenchymal gliomas(F=21.8,P<0.01),and the BICD1 expression level in the mesenchymal glioma was the highest and the one in the proneural glioma was the lowest.The BICD1 expression level was correlated with classical molecular markers of malignant degrees of glioma,such as isocitrate dehydrogenase 1(IDH1)mutation,combined deletion of chromosome 1p19q and phosphatase and tensin homolog deleted on chromosome ten(PTEN)mutation.The expression level of BICD1 was significantly lower in the IDH1 mutation glioma samples than that in the wildtype samples(t=7.769,P<0.01).Conclusion BICD1 may be a potential biomarker for grade progress and malignant progression of low-grade glioma.