Wan Luying, Liu Ziyi, Li Shunyao, Gao Zhe
Department of Oncology, Molecular Oncology Research Institute, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Fuzhou, 350005, China.
Department of Oncology, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
Acta Neurochir (Wien). 2025 May 17;167(1):144. doi: 10.1007/s00701-025-06548-x.
PURPOSE: Although IDH-mutant astrocytomas exhibit more favorable survival outcomes compared to their IDH-wildtype counterparts, therapeutic failure in recurrent cases persists as a significant clinical challenge. The objective of this study is to identify genes associated with recurrence in IDH-mutant astrocytoma and to elucidate their expression pattern, biological functions, and prognostic value. METHODS: RNA-sequencing data of patients with IDH-mutant astrocytoma were collected from 96 cases in the Chinese Glioma Genome Atlas (CGGA) database, 150 cases in CGGA2019 and 222 cases in The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were identified using unpaired t-tests between recurrent and primary IDH-mutant astrocytoma. GO and KEGG analyses were performed to analyze these DEGs. Pearson correlation analysis was employed to assess the correlation between High mobility group AT-hook 2 (HMGA2) and genes associated with cell invasion and extracellular matrix components. Kaplan-Meier analyses and univariate and multivariate Cox regression analyses were conducted to assess the prognosis. RESULTS: HMGA2 was highly expressed in patients with recurrent IDH-mutant astrocytoma in comparison to those with primary IDH-mutant astrocytoma. Patients with higher HMGA2 expression are more likely to have high-grade gliomas and to be in the O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation group. Functional enrichment and correlation analyses revealed that HMGA2 is closely related to extracellular matrix content and cell migration and invasion ability. HMGA2 is an independent prognostic factor associated with poor prognosis in patients with IDH-mutant astrocytoma. CONCLUSIONS: HMGA2 was highly expressed in recurrent IDH-mutant astrocytoma, with higher expression levels associated with increased cell migration and invasion abilities. HMGA2 has the potential to serve as a biomarker for poor prognosis and may represent an effective therapeutic target in the treatment of IDH-mutant astrocytoma.
目的：尽管与异柠檬酸脱氢酶（IDH）野生型星形细胞瘤相比，IDH突变型星形细胞瘤表现出更有利的生存结果，但复发病例的治疗失败仍然是一个重大的临床挑战。本研究的目的是确定与IDH突变型星形细胞瘤复发相关的基因，并阐明其表达模式、生物学功能和预后价值。 方法：从中国胶质瘤基因组图谱（CGGA）数据库中的96例、CGGA2019中的150例以及癌症基因组图谱（TCGA）中的222例患者收集IDH突变型星形细胞瘤患者的RNA测序数据。使用未配对t检验在复发性和原发性IDH突变型星形细胞瘤之间鉴定差异表达基因（DEG）。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析以分析这些DEG。采用Pearson相关分析评估高迁移率族AT钩蛋白2（HMGA2）与细胞侵袭相关基因和细胞外基质成分之间的相关性。进行Kaplan-Meier分析以及单变量和多变量Cox回归分析以评估预后。 结果：与原发性IDH突变型星形细胞瘤患者相比，HMGA2在复发性IDH突变型星形细胞瘤患者中高表达。HMGA2表达较高的患者更有可能患有高级别胶质瘤并且属于O6-甲基鸟嘌呤-DNA甲基转移酶启动子（MGMTp）甲基化组。功能富集和相关性分析表明，HMGA2与细胞外基质含量以及细胞迁移和侵袭能力密切相关。HMGA2是与IDH突变型星形细胞瘤患者预后不良相关的独立预后因素。 结论：HMGA2在复发性IDH突变型星形细胞瘤中高表达，较高的表达水平与细胞迁移和侵袭能力增加相关。HMGA2有可能作为预后不良的生物标志物，并且可能代表IDH突变型星形细胞瘤治疗中的有效治疗靶点。
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