Enrichment of Aldolase C Correlates with Low Non-Mutated IDH1 Expression and Predicts a Favorable Prognosis in Glioblastomas
Enrichment of Aldolase C Correlates with Low Non-Mutated IDH1 Expression and Predicts a Favorable Prognosis in Glioblastomas
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DOI：
10.3390/cancers11091238
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发表时间：
2019-09-01
期刊：
影响因子：
5.2
通讯作者：
Tsai, Wen-Chivan
中科院分区：
文献类型：
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作者：
Chang, Yu-Chan;Tsai, Hsing-Fang;Tsai, Wen-Chivan
醛缩酶家族是参与糖酵解过程的主要酶之一。醛缩酶C（ALDOC）属于醛缩酶家族，存在于正常脑组织中，负责损伤组织的修复。然而，ALDOC在胶质母细胞瘤中的作用仍不清楚。在这项研究中，我们在计算机数据库中进行数据挖掘，以评估胶质母细胞瘤患者队列中醛缩酶家族成员的mRNA表达，以确定其预后价值。之后，我们还进行了免疫组织化学染色（IHC）分析，以评估ALDOC在胶质母细胞瘤组织中的蛋白表达水平。根据癌症基因组图谱（TCGA）数据库分析，观察到正常脑组织中的mRNA表达水平高于胶质母细胞瘤。此外，与低级别胶质瘤相比，ALDOC表达在高级别胶质母细胞瘤中显著下调。此外，ALDOC的表达水平与胶质母细胞瘤的分子亚型和复发状态有关。相比之下，醛缩酶A（ALDOA）和醛缩酶B（ALDO B）在胶质母细胞瘤队列中未显示出显著的预后影响。此外，我们还证明了ALDOC mRNA和蛋白表达与胶质母细胞瘤患者队列中非突变IDH1表达呈负相关。此外，低ALDOC和高非突变IDH1表达的一致性预测胶质母细胞瘤患者的预后更差，与单独提供的上述每种测试相比。进一步阐明了ALDOC和IDH1可能的调控机制。我们的研究结果支持ALDOC在胶质母细胞瘤中的高表达，这可能意味着IDH1的突变状态，间充质亚型的可能性较小，并预测良好的预后。
The aldolases family is one of the main enzymes involved in the process of glycolysis. Aldolase C (ALDOC), which belongs to the aldolase family, is found in normal brain tissue and is responsible for the repair of injured tissue. However, the role of ALDOC in glioblastoma remains unclear. In this study, we data-mined in silico databases to evaluate aldolase family members' mRNA expression in glioblastoma patient cohorts for determining its prognostic values. After that, we also performed immunohistochemical stain (IHC) analysis to evaluate protein expression levels of ALDOC in glioblastoma tissues. From The Cancer Genome Atlas (TCGA) database analyses, higher mRNA expression levels in normal brain tissue compared to glioblastoma was observed. In addition, compared to low-grade glioma, ALDOC expression was significantly downregulated in high-grade glioblastoma. Besides, the expression level of ALDOC was associated with molecular subtypes of glioblastomas and recurrent status in several data sets. In contrast, aldolase A (ALDOA) and aldolase B (ALDOB) revealed no significant prognostic impacts in the glioblastoma cohorts. Furthermore, we also proved that ALDOC mRNA and protein expression inversely correlated with non-mutated IDH1 expressions in glioblastoma patient cohorts. Additionally, the concordance of low ALDOC and high non-mutated IDH1 expressions predicted a stronger poor prognosis in glioblastoma patients compared to each of above tests presented alone. The plausible ALDOC and IDH1 regulatory mechanism was further elucidated. Our results support high ALDOC expression in glioblastomas that might imply the mutated status of IDH1, less possibility of mesenchymal subtype, and predict a favorable prognosis.