摘要
目的探讨CDKN2A基因mRNA表达水平对胶质母细胞瘤(GBM)患者预后评价的意义。方法利用GBM在线数据库中的临床资料和芯片数据,通过Kaplan—Meier分析和Cox回归分析,探讨并验证CDKN2A基因mRNA表达与GBM患者总生存(OS)的关系。结果在癌症和肿瘤基因图谱计划(TCGA)训练组(358例)中,CDKN2A基因mRNA低表达患者的预后差于高表达的患者,其中位OS分别为13.9个月(95%C112.4~15.4个月)和18.0个月(95%C115.0~21.0个月)(P〈0.001)。在脑肿瘤分子数据库(REMBRANDT)病例组(187例)中,CDKN2A基因低表达患者的预后差于高表达患者,其中位OS分别为11.8个月(95%C17.3~16.4个月)和16.6个月(95%CI13.3~19.8个月)(P:0.019)。在GSEl6011数据库病例组(147例)中,CDKN2A基因低表达患者的预后差于高表达患者,其中位OS分别为8.4个月(95%CI6.2~10.5个月)和1L9个月(95%CI8.3~15.6个月)(P=0.005)。多因素Cox回归分析表明CDKN2A基因mRNA表达分组是GBM患者独立的预后因素。联合分层分析表明CDKN2A基因mRNA表达分组能够进一步优化经典的MGMT启动子甲基化分组和G.CIMP表型/IDHl突变型的分组。结论CDKN2A基因mRNA表达水平与GBM患者的临床预后密切相关,是评价GBM预后的独立因素。将CDKN2A基因mRNA表达分组引入现有的GBM分子分型能够进一步细化患者的预后分层。
Objective To investigate the prognostic value of CDKN2A mRNA in glioblastoma (GBM). Methods CDKN2A gene mRNA data were obtained from three different GBM database online (TCGA, REMBARNDT and GSE16011). The correlations between overall survival (OS) and CDKN2A expression were analyzed by Kaplan-Meier method and multivariate Cox regression analysis. Results In the TCGA database (n = 358), patients with high CDKN2A mRNA level got longer OS than those with low expression level [median OS: 18.0 months (95 % CI 15.0-21.0 months) vs 13.9 months (95 % CI 12.4-15.4 months), P = 0.001]. In another two validation datasets, patients with high CDKN2A mRNA level had longer OS than those with low expression level [median OS in REMBRANT: 16.6 months (95 % CI 13.3-19.8 months) vs 11.8 months (95 % CI 7.3-16.4 months), P = 0.019; in GSE16011:11.9 months (95 % CI 8.3-15.6 months) vs 8.4 months (95 % CI 6.2-10.5 months), P : 0.005]. CDKN2A mRNA level was an independent prognostic factor for GBM. The combination of CDKN2A mRNA expression with MGMT promoter methylation status or G-CIMP status/IDH1 mutations provided an optimized prognostic factor in GBM patients. Conclusion The CDKN2A mRNA has prognostic value in GBM patients, which provided an optimized stratification strategy based on multiple biomarkers.
出处
《肿瘤研究与临床》
CAS
2015年第11期766-770,共5页
Cancer Research and Clinic
基金
国家自然科学基金青年科学基金(81402049)