目的通过对脑胶质瘤基因表达谱的分析,找出在脑胶质瘤恶性进展过程中可能起作用的基因。方法收集220例脑胶质瘤组织标本(低级别97例,高级别123例),提取肿瘤组织RNA并进行微阵列芯片分析。应用免疫组织化学染色方法验证基因芯片结果。结果在高级别脑胶质瘤组织中表达水平上调前5位的基因为IGFBP-2、CKLF、PTrG1、OSTCL和PTYG2;在低级别脑胶质瘤组织中表达水平上调前5位的基因为SEC31B、RRP7B、HOOK3、SNRPN和CSMD3。采用免疫组化方法检测IGFBP-2的表达,高级别组的免疫染色强度明显高于低级别组。通过基因本体论分析发现:CKLF可以提高细胞迁移能力、促进细胞增殖;CDKN3调节细胞有丝分裂周期,促进由G1到s期的过度;IGFBP-2与细胞增殖、耐药性相关,调节生长激素作用,同时调节IGFR通路;PTTG1和PTGG2与细胞有丝分裂周期相关;RPS7调节RNA的合成和翻译;TK1参与DNA的代谢、DNA的复制过程同时和调节细胞对药物的代谢。结论通过基因芯片发现系列与脑胶质瘤恶性进展相关的基因,为脑胶质瘤的基因治疗提供潜在靶点。
Objective To employ whole-genome messenger RNA profiling to identify the genes involved in malignant progression in glioma. Methods The whole genome expressed genes were profiled in 220 glioma patients from the Chinese Glioma Genome Atlas (97 LGGs and 123 HGGs). The differential expressed genes between LGG and HGG were identified by SAM analysis. Microarray data were validated by immunohistochemistry. Results Among all the detected genes, the genes up-regulated mostly in high-grade glioma were IGFBP-2, CKLF, PTTG1, OSTCL and FITG2 while those down-regulated mostly SEC31, RRP7B, HOOK3, SNRPN and CSMD3. Validation of IGFBP-2 with immunohistochemical staining showed a good correlation with the microarray data. Conclusion A panel of potential genes of malignant transformation may serve as future targets of gene therapy for glioma.