Altered capicua transcriptional repressor gene expression exhibits distinct prognostic value for isocitrate dehydrogenase-mutant oligodendroglial tumors

改变的 Capicua 转录抑制基因表达对异柠檬酸脱氢酶突变少突胶质细胞肿瘤具有明显的预后价值

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作者:Fuxin Han, Jinsong Zhang, Shanbo Ma, Xiaoyan Chen, Weiping Liu, Xiaosheng He, Zhou Fei, Yangang Wang

Abstract

To evaluate the prognostic significance of the altered expression of capicua transcriptional repressor (CIC) in isocitrate dehydrogenase (IDH)-mutant oligodendroglial tumors, a cohort of 54 IDH-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 IDH-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 IDH-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 IDH-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.

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