HMGA1作为胶质瘤的预后生物标志物：来自巴基斯坦队列的表达模式、生存相关性及临床见解

HMGA1 as a prognostic biomarker for gliomas: expression patterns, survival correlations, and clinical insights from a Pakistani cohort.

作者信息

Din Siraj Ud, Sufiyan Sufiyan, Shah Asif Ali, Fatima Hania, Salam Hira, Naeem Sana, Laghari Altaf Ali, Kayani Hammad Afzal, Enam Syed Ather, Mughal Nouman

机构信息

Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan.

Department of Biosciences, The Shaheed Zulfikar Ali Bhutto Institute of Science and Technology, Karachi, Pakistan.

出版信息

J Neurooncol. 2025 Apr 28. doi: 10.1007/s11060-025-05031-y.

DOI:10.1007/s11060-025-05031-y

PMID:40293672

Abstract

PURPOSE

High-Mobility Group A1 (HMGA1) is a chromatin-associated protein involved in regulating key cellular processes, including DNA transcription, replication, recombination, and repair. It is highly expressed during embryogenesis and reactivated in various cancers, where it contributes to tumor progression and metastasis. We investigated the prognostic significance of HMGA1 gene expression in gliomas by comparing its expression in normal brain tissue and different glioma grades.

METHODS

Real-time quantitative PCR (qPCR) was performed on 75 glioma samples obtained from Aga Khan University Hospital (Pakistan), along with 10 Normal Adjacent Tissue (NAT) samples. The correlation between HMGA1 expression and prognosis was evaluated using Kaplan-Meier (KM) plotter in glioma patients. Statistical analyses were conducted using the R platform and further validated through the online database Chinese Glioma Genome Atlas (CGGA) using online tools.

RESULTS

HMGA1 expression was significantly upregulated in gliomas compared to NAT (p < 0.001) and increased with tumor grade (p = 0.015). High HMGA1 expression correlated with Ki-67 levels and was associated with worse survival (p = 0.0014). Patients with elevated HMGA1 had a 3.5-fold higher mortality risk (95% CI: 1.5-7.9, p = 0.003). ROC analysis yielded an AUC of 0.752, indicating its potential prognostic value.

CONCLUSION

HMGA1 overexpression is associated with poor prognosis in gliomas, suggesting its potential as a prognostic marker. However, further validation is needed to confirm its clinical utility.

摘要

目的

高迁移率族蛋白A1（HMGA1）是一种与染色质相关的蛋白质，参与调控关键的细胞过程，包括DNA转录、复制、重组和修复。它在胚胎发育过程中高度表达，并在各种癌症中重新激活，促进肿瘤进展和转移。我们通过比较HMGA1基因在正常脑组织和不同胶质瘤分级中的表达，研究其在胶质瘤中的预后意义。

方法

对从阿迦汗大学医院（巴基斯坦）获取的75例胶质瘤样本以及10例正常相邻组织（NAT）样本进行实时定量PCR（qPCR）。使用Kaplan-Meier（KM）绘图仪评估胶质瘤患者中HMGA1表达与预后的相关性。使用R平台进行统计分析，并通过在线数据库中国胶质瘤基因组图谱（CGGA）使用在线工具进一步验证。

结果

与NAT相比，胶质瘤中HMGA1表达显著上调（p < 0.001），并随肿瘤分级增加而升高（p = 0.015）。高HMGA1表达与Ki-67水平相关，且与较差的生存率相关（p = 0.0014）。HMGA1升高的患者死亡风险高3.5倍（95% CI：1.5 - 7.9，p = 0.003）。ROC分析得出AUC为0.752，表明其潜在的预后价值。