Prognostic Value of PFKFB3 to PFKFB4 mRNA Ratio in Patients With Primary Glioblastoma (IDH-Wildtype)
Prognostic Value of PFKFB3 to PFKFB4 mRNA Ratio in Patients With Primary Glioblastoma (IDH-Wildtype)
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DOI：
10.1093/jnen/nlz067
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发表时间：
2019-09-01
影响因子：
3.2
通讯作者：
Eschrich, Klaus
中科院分区：
文献类型：
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作者：
Kessler, Renate;Fleischer, Michael;Eschrich, Klaus
胶质母细胞瘤的一个标志是高水平的有氧糖酵解。PFKFB 3和PFKFB 4是调节性糖酵解酶，在胶质母细胞瘤中过表达。选择性抑制这些酶已经成为肿瘤治疗的新方法。我们研究了66例不同恶性程度的星形细胞肿瘤中PFKFB 3和PFKFB 4 mRNA表达的比例。在所有分析的肿瘤中，PFKFB 3 mRNA水平显著高于PFKFB 4。IDH-野生型胶质母细胞瘤显示PFKFB 3与PFKFB 4 mRNA比率（7.7：1）低于IDH-突变型低级别星形细胞瘤（36.5：1），表明比率依赖于恶性程度。在表现出PFKFB 3基因位点杂合性缺失（洛）的IDH-野生型胶质母细胞瘤中，PFKFB 3 mRNA水平的降低伴随着PFKFB 4 mRNA水平的降低，但PFKFB 3与PFKFB 4 mRNA的比例在有或无PFKFB 3洛的肿瘤之间没有差异。具有高于平均7.7：1的高PFKFB 3与PFKFB 4 mRNA比率的IDH-野生型原发性胶质母细胞瘤患者的总生存时间（14个月）显著长于具有较低比率的患者（9个月）。我们的研究结果表明，PFKFB 3与PFKFB 4的低表达比例是IDH-野生型原发性胶质母细胞瘤患者预后不良的因素，PFKFB 3和PFKFB 4可能是星形细胞瘤和胶质母细胞瘤治疗的有希望的靶点。
A hallmark of glioblastoma is the high level of aerobic glycolysis. PFKFB3 and PFKFB4 are regulatory glycolytic enzymes, which are overexpressed in glioblastomas. Selective inhibition of these enzymes has emerged as a new approach in tumor therapy. We investigated the ratios of PFKFB3 to PFKFB4 mRNA expression in 66 astrocytic tumors of different malignancy grades. PFKFB3 mRNA levels were considerably higher than those of PFKFB4 in all analyzed tumors. IDH-wildtype glioblastomas showed lower PFKFB3 to PFKFB4 mRNA ratios (7.7:1) than IDH-mutant lowgrade astrocytomas (36.5:1), indicating a dependency of the ratio on malignancy grade. In IDH-wildtype glioblastomas exhibiting loss of heterozygosity (LOH) of the PFKFB3 gene locus, the decrease of PFKFB3 mRNA levels was accompanied by lower PFKFB4 mRNA levels, but the PFKFB3 to PFKFB4 mRNA ratio did not differ between tumors with or without PFKFB3 LOH. IDH-wildtype primary glioblastoma patients with high PFKFB3 to PFKFB4 mRNA ratios above the average of 7.7:1 had a significantly longer overall survival time (14 months) than patients with lower ratios (9 months). Our results indicate that low PFKFB3 to PFKFB4 expression ratio is a poor prognostic factor in patients with IDH-wildtype primary glioblastoma and that PFKFB3 and PFKFB4 might represent promising targets for astrocytoma and glioblastoma treatment.