Systematically profiling the expression of eIF3 subunits in glioma reveals the expression of eIF3i has prognostic value in IDH-mutant lower grade glioma
Systematically profiling the expression of eIF3 subunits in glioma reveals the expression of eIF3i has prognostic value in IDH-mutant lower grade glioma
复制标题
系统分析神经胶质瘤中 eIF3 亚基的表达揭示 eIF3i 的表达在 IDH 突变的低级别神经胶质瘤中具有预后价值
DOI：
10.1186/s12935-019-0867-1
复制
发表时间：
2019-06-04
影响因子：
5.8
通讯作者：
Wang, Yong-Zhi
中科院分区：
文献类型：
--
作者：
Chai, Rui-Chao;Wang, Ning;Wang, Yong-Zhi
真核起始因子3 （eIF3）亚基的异常表达在肿瘤发生和进展中起着关键作用，并且在癌症中也具有潜在的预后价值。然而，eIF3亚基在胶质瘤中的表达及其临床意义尚不清楚。方法从中国胶质瘤基因组图谱（CGGA） （n= 272）和肿瘤基因组图谱（TCGA） （n= 595）中获取胶质瘤患者eIF3的表达数据。采用Cox回归、受试者工作特征（ROC）曲线和Kaplan-Meier分析研究预后价值。基因肿瘤学（GO）和基因集富集分析（GSEA）用于功能预测。结果在CGGA和TCGA数据集中，eIF3d、eIF3e、eIF3f、eIF3h和eif31的表达水平与胶质瘤IDH突变状态高度相关。eIF3b、eIF3i、eIF3k和eIF3m的表达随肿瘤分级而升高，且与较差的总生存率相关[All Hazard ratio (HR) bbb1, P < 0.05]。而eIF3a和eIF3l在高级别胶质瘤中的表达降低，且与较好的总生存率相关（HR < 1, P < 0.05）。重要的是，eIF3i（位于染色体1p）和eIF3k（位于染色体19q）的表达是CGGA中两个最高的危险因素[eIF3i HR = 2.068 (1.425-3.000)]；eIF3k HR = 1.737 (1.166 ~ 2.588), TCGA [eIF3i HR = 1.841 (1.642 ~ 2.064)]；eIF3k HR = 1.521(1.340-1.726)]数据库。在eIF3i、eIF3k单独或联合作用中，eIF3i的表达在胶质瘤各病理亚组的生存分层中更为稳健。eIF3i的表达是idh突变型低级别胶质瘤（LGG）的独立预后因素，也可以预测idh突变型LGG的1p/19q编码状态。最后，GO和GSEA分析显示，eIF3i的表达升高与细胞增殖、mRNA加工、翻译、T细胞受体信号转导、NF-κB信号转导等生物学过程显著相关。结论sour研究揭示了胶质瘤进展过程中eIF3i的表达变化，强调了eIF3i在idh突变型LGG中的预后价值。
BackgroundAbnormal expression of the eukaryotic initiation factor 3 (eIF3) subunits plays critical roles in tumorigenesis and progression, and also has potential prognostic value in cancers. However, the expression and clinical implications of eIF3 subunits in glioma remain unknown.MethodsExpression data of eIF3 for patients with gliomas were obtained from the Chinese Glioma Genome Atlas (CGGA) (n= 272) and The Cancer Genome Atlas (TCGA) (n= 595). Cox regression, the receiver operating characteristic (ROC) curves and Kaplan–Meier analysis were used to study the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were utilized for functional prediction.ResultsIn both the CGGA and TCGA datasets, the expression levels of eIF3d, eIF3e, eIF3f, eIF3h and eIF3l highly were associated with the IDH mutant status of gliomas. The expression of eIF3b, eIF3i, eIF3k and eIF3m was increased with the tumor grade, and was associated with poorer overall survival [All Hazard ratio (HR) > 1 and P < 0.05]. By contrast, the expression of eIF3a and eIF3l was decreased in higher grade gliomas and was associated with better overall survival (Both HR < 1 and P < 0.05). Importantly, the expression of eIF3i (located on chromosome 1p) and eIF3k (Located on chromosome 19q) were the two highest risk factors in both the CGGA [eIF3i HR = 2.068 (1.425–3.000); eIF3k HR = 1.737 (1.166–2.588)] and TCGA [eIF3i HR = 1.841 (1.642–2.064); eIF3k HR = 1.521 (1.340–1.726)] databases. Among eIF3i, eIF3k alone or in combination, the expression of eIF3i was the more robust in stratifying the survival of glioma in various pathological subgroups. The expression of eIF3i was an independent prognostic factor in IDH-mutant lower grade glioma (LGG) and could also predict the 1p/19q codeletion status of IDH-mutant LGG. Finally, GO and GSEA analysis showed that the elevated expression of eIF3i was significantly correlated with the biological processes of cell proliferation, mRNA processing, translation, T cell receptor signaling, NF-κB signaling and others.ConclusionsOur study reveals the expression alterations during glioma progression, and highlights the prognostic value of eIF3i in IDH-mutant LGG.