高通量数据分析DNA损伤诱导转录样蛋白4在脑多形性胶质母细胞瘤中表达及临床意义

Clinical significance of DNA damage-inducible transcript 4-like in glioblastoma multiforme analyzed using internet datasets

目的探讨DNA损伤诱导转录样蛋白4(DDIT4L)在人脑多形性胶质母细胞瘤(GBM)中的表达与患者预后的关系及相关机制。方法分别从癌症基因组图谱(TCGA)和人类肿瘤相关基因表达汇编(GEO)数据库下载GBM的RNASeq V2数据,以及GBM样本数据集GSE7696的系列矩阵数据。应用Kaplan-Meier和多因素COX逐步回归分析方法确定DDIT4L的预后价值,采用基因集富集分析方法分析DDIT4L相关的信号通路。结果 DDIT4L高表达是提示GBM术后患者预后不良的独立因素,其高表达与烟酸-烟酰胺代谢、组氨酸代谢、氮代谢、苯丙氨酸代谢相关通路增强有关。结论 DDIT4L高表达的GBM患者预后不良,可能通过对GBM中的烟酸-烟酰胺、组氨酸、氮或苯丙氨酸代谢的调节而发挥促肿瘤作用。

Objective To clarify the clinical significance and the related mechanism of DNA damage-inducible transcript 4-like（ DDiT4L） in glioblastoma multiforme（ GBM）. Methods RNASeq V2 data from The Cancer Genome Atlas（ TCGA） and series matrix data of GSE7696 from The Gene Expression Omnibus（ GEO） database were downloaded,respectively. The prognosis significance of DDiT4L expression was sequentially analyzed by Kaplan-Meier and multivariate COX analysis. The functional pathways related with DDiT4L expression was identified by Gene Sets Enrichment Analysis（ GSEA）. Results The over-expression of DDiT4L was the independent predictor for poorer prognosis. Furthermore,genes up-regulated in nicotinate and nicotinamide,histidine,nitrogen,and phenylalanine metabolism pathways were enriched in samples with high DDiT4L expression. Conclusion Over-expression of DDiT4L indicates poor prognosis of GBM patients. And the genes up-regulated in nicotinate and nicotinamide,histidine,nitrogen,and phenylalanine metabolism pathways might be the related mechanism.