{"title":"HMGA2 is an independent prognostic indicator and a potential therapeutic target for IDH-mutant astrocytoma","authors":"Luying Wan, Ziyi Liu, Shunyao Li, Zhe Gao","doi":"10.1007/s00701-025-06548-x","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>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.</p><h3>Methods</h3><p>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.</p><h3>Results</h3><p>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.</p><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":7370,"journal":{"name":"Acta Neurochirurgica","volume":"167 1","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00701-025-06548-x.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Neurochirurgica","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00701-025-06548-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
The journal "Acta Neurochirurgica" publishes only original papers useful both to research and clinical work. Papers should deal with clinical neurosurgery - diagnosis and diagnostic techniques, operative surgery and results, postoperative treatment - or with research work in neuroscience if the underlying questions or the results are of neurosurgical interest. Reports on congresses are given in brief accounts. As official organ of the European Association of Neurosurgical Societies the journal publishes all announcements of the E.A.N.S. and reports on the activities of its member societies. Only contributions written in English will be accepted.
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