Department of Neurosurgery, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Sci Rep. 2022 Sep 29;12(1):16277. doi: 10.1038/s41598-022-20613-w.
Glioblastoma is the most common brain tumor with dismal outcomes in adults. Metabolic remodeling is now widely acknowledged as a hallmark of cancer cells, but glioblastoma-specific metabolic pathways remain unclear. Here we show, using a large-scale targeted proteomics platform and integrated molecular pathway-level analysis tool, that the de novo pyrimidine synthesis pathway and serine synthesis pathway (SSP) are the major enriched pathways in vivo for patients with glioblastoma. Among the enzymes associated with nucleotide synthesis, RRM1 and NME1 are significantly upregulated in glioblastoma. In the SSP, SHMT2 and PSPH are upregulated but the upstream enzyme PSAT1 is downregulated in glioblastoma. Kaplan-Meier curves of overall survival for the GSE16011 and The Cancer Genome Atlas datasets revealed that high SSP activity correlated with poor outcome. Enzymes relating to the pyrimidine synthesis pathway and SSP might offer therapeutic targets for new glioblastoma treatments.
胶质母细胞瘤是成人中最常见的脑肿瘤，预后极差。代谢重编程现在被广泛认为是癌细胞的一个标志，但胶质母细胞瘤特异性的代谢途径仍不清楚。在这里，我们使用大规模的靶向蛋白质组学平台和综合的分子通路水平分析工具，表明从头嘧啶合成途径和丝氨酸合成途径（SSP）是体内胶质母细胞瘤患者主要富集的途径。在与核苷酸合成相关的酶中，RRM1 和 NME1 在胶质母细胞瘤中显著上调。在 SSP 中，SHMT2 和 PSPH 上调，但 PSAT1 这种上游酶在胶质母细胞瘤中下调。GSE16011 和癌症基因组图谱数据集的总体生存 Kaplan-Meier 曲线显示，高 SSP 活性与不良预后相关。与嘧啶合成途径和 SSP 相关的酶可能为新的胶质母细胞瘤治疗提供治疗靶点。
