Han Fuxin, Zhang Jinsong, Ma Shanbo, Chen Xiaoyan, Liu Weiping, He Xiaosheng, Fei Zhou, Wang Yangang
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Oncol Lett. 2018 Feb;15(2):1459-1468. doi: 10.3892/ol.2017.7460. Epub 2017 Nov 21.
To evaluate the prognostic significance of the altered expression of capicua transcriptional repressor (CIC) in isocitrate dehydrogenase ()-mutant oligodendroglial tumors, a cohort of 54 -mutant oligodendroglial tumors (designated as the Xijing cohort) were examined by immunohistochemistry (IHC), and two public expression data sets from The Cancer Genome Atlas (TCGA; n=265) and the Gene Expression Omnibus (GEO; n=45) were analyzed in the present study. The prognostic value was evaluated by survival analysis and Cox hazards models. Overall survival (OS) was investigated with Kaplan-Meier curves and log-rank tests. Gene set enrichment analysis (GSEA) was also performed to characterize the functional profiles of each subgroup. It was revealed that in -mutant, 1p/19q co-deleted oligodendroglial tumors, higher CIC expression (at mRNA and protein levels) was associated with a more favorable OS time (log-rank P-values: TCGA, P=0.034; GEO, P=0.012; Xijing cohort, P=0.029). By contrast, among -mutant, 1p/19q intact tumors, higher CIC expression was associated with poorer OS time (log-rank P-values: TCGA, P=0.007; GEO, P=0.017; Xijing cohort, P=0.012). To the best of our knowledge, this is the first study demonstrating the distinct prognostic value of altered CIC expression with regard to the 1p/19q status among -mutant oligodendroglial tumors. The dual roles of CIC may be influenced by its transcriptional regulatory activity and the consequent functional profiles. Additionally, a simple risk classification scheme based on CIC expression alone is proposed for the optimal prediction of prognosis in patients with oligodendroglial tumors.
为评估异柠檬酸脱氢酶（IDH）突变型少突胶质细胞瘤中capicua转录抑制因子（CIC）表达改变的预后意义，本研究采用免疫组织化学（IHC）检测了54例IDH突变型少突胶质细胞瘤队列（命名为西京队列），并分析了来自癌症基因组图谱（TCGA；n = 265）和基因表达综合数据库（GEO；n = 45）的两个公开表达数据集。通过生存分析和Cox风险模型评估预后价值。采用Kaplan-Meier曲线和对数秩检验研究总生存期（OS）。还进行了基因集富集分析（GSEA）以表征每个亚组的功能特征。结果显示，在IDH突变、1p/19q共缺失的少突胶质细胞瘤中，较高的CIC表达（在mRNA和蛋白质水平）与更有利的OS时间相关（对数秩P值：TCGA，P = 0.034；GEO，P = 0.012；西京队列，P = 0.029）。相比之下，在IDH突变、1p/19q完整的肿瘤中，较高的CIC表达与较差的OS时间相关（对数秩P值：TCGA，P = 0.007；GEO，P = 0.017；西京队列，P = 0.012）。据我们所知，这是第一项证明IDH突变型少突胶质细胞瘤中CIC表达改变对1p/19q状态具有不同预后价值的研究。CIC的双重作用可能受其转录调节活性及相应功能特征的影响。此外，还提出了一种仅基于CIC表达的简单风险分类方案，用于少突胶质细胞瘤患者预后的最佳预测。
