Chang Yu-Chan, Tsai Hsing-Fang, Huang Shang-Pen, Chen Chi-Long, Hsiao Michael, Tsai Wen-Chiuan
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
Cancers (Basel). 2019 Aug 23;11(9):1238. doi: 10.3390/cancers11091238.
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.
醛缩酶家族是参与糖酵解过程的主要酶类之一。醛缩酶C(ALDOC)属于醛缩酶家族,存在于正常脑组织中,负责受损组织的修复。然而,ALDOC在胶质母细胞瘤中的作用仍不清楚。在本研究中,我们通过对计算机数据库进行数据挖掘,以评估醛缩酶家族成员在胶质母细胞瘤患者队列中的mRNA表达,从而确定其预后价值。之后,我们还进行了免疫组织化学染色(IHC)分析,以评估胶质母细胞瘤组织中ALDOC的蛋白表达水平。通过癌症基因组图谱(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,高级别胶质母细胞瘤中ALDOC的表达明显下调。此外,在多个数据集中,ALDOC的表达水平与胶质母细胞瘤的分子亚型和复发状态相关。相比之下,醛缩酶A(ALDOA)和醛缩酶B(ALDOB)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,在胶质母细胞瘤患者队列中,ALDOC的mRNA和蛋白表达与未突变的异柠檬酸脱氢酶1(IDH1)表达呈负相关。此外,与单独进行上述每项检测相比,低ALDOC和高未突变IDH1表达的一致性预测胶质母细胞瘤患者的预后更差。我们进一步阐明了ALDOC和IDH1可能的调控机制。我们的结果支持胶质母细胞瘤中高ALDOC表达可能意味着IDH1的突变状态、间充质亚型的可能性较小,并预示着良好的预后。