Background: Glioblastoma (GBM) is the most aggressive type of human brain tumor with a poor prognosis and a low survival rate. Secreted proteins from tumors are recently considered as important modulators to promote tumorigenesis by communicating with microenvironments. Repulsive guidance molecule A (RGMA) was initially characterized as an axon guidance molecule after secretion in the brain during embryogenesis but has not been studied in GBM. In this study, we investigated secreted gene expression patterns and the correlation between RGMA expression and prognosis in GBM using in silico analysis.
Methods: RGMA mRNA levels in normal human astrocyte (NHA), human glioma cells, and GBM patient-derived glioma stem cells (GSCs) were assessed by qRT‐PCR. Patient survival analysis was performed with the Kaplan–Meier curve and univariate and multivariate analyses using publicly available datasets. The predictive roles of RGMA in progressive malignancy were evaluated using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).
Results: RGMA mRNA expression was elevated in glioma cells and GSCs compared with NHA and correlated with unfavorable prognosis in glioma patients. Thus, RGMA could serve as an independent predictive factor for GBM. Furthermore, the increased levels of RGMA expression and its putative receptor, neogenin (NEO1), were associated with poor patient survival rates in GBM.
Conclusion: We identified RGMA as an independent prognostic biomarker for progressive malignancy in glioblastoma and address the possibilities to develop novel therapeutic strategies against glioblastoma.



中文翻译：

---

RGMA 表达升高预示胶质母细胞瘤患者预后不良

背景：胶质母细胞瘤（GBM）是最具侵袭性的人类脑肿瘤，预后差，存活率低。来自肿瘤的分泌蛋白最近被认为是通过与微环境交流来促进肿瘤发生的重要调节剂。排斥性引导分子 A (RGMA) 最初被描述为胚胎发育过程中大脑分泌后的轴突引导分子，但尚未在 GBM 中进行研究。在这项研究中，我们使用计算机分析研究了分泌基因表达模式以及 RGMA 表达与 GBM 预后之间的相关性。
方法： RGMA通过 qRT-PCR 评估正常人星形胶质细胞 (NHA)、人胶质瘤细胞和 GBM 患者来源的胶质瘤干细胞 (GSC) 中的 mRNA 水平。使用公开可用的数据集使用 Kaplan-Meier 曲线和单变量和多变量分析进行患者生存分析。使用基因本体论 (GO)、京都基因和基因组百科全书 (KEGG) 和基因集富集分析 (GSEA) 评估 RGMA 在进行性恶性肿瘤中的预测作用。
结果： RGMA与 NHA 相比，胶质瘤细胞和 GSCs 中的 mRNA 表达升高，并且与胶质瘤患者的不良预后相关。因此，RGMA 可以作为 GBM 的独立预测因素。此外，RGMA 表达水平的增加及其推定的受体 neogenin (NEO1) 与 GBM 患者的低存活率有关。
结论：我们将 RGMA 确定为胶质母细胞瘤进行性恶性肿瘤的独立预后生物标志物，并探讨了开发针对胶质母细胞瘤的新治疗策略的可能性。