Jue Toni Rose, Descallar Joseph, Pham Vu Viet Hoang, Bell Jessica Lilian, Shai-Hee Tyler, Cazzolli Riccardo, Nagabushan Sumanth, Koh Eng-Siew, Vittorio Orazio
School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia 1466.
Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Randwick, New South Wales, Australia 1466.
Neurooncol Adv. 2024 Dec 23;7(1):vdae233. doi: 10.1093/noajnl/vdae233. eCollection 2025 Jan-Dec.
Adult-type diffuse gliomas encompass nearly a quarter of all primary tumors found in the CNS, including astrocytoma, oligodendroglioma, and glioblastoma. Histopathological tumor grade and molecular profile distinctly impact patient survival. Despite treatment advancements, patients with recurrent glioma have a very poor clinical outcome, warranting improved risk stratification to determine therapeutic interventions. Various studies have shown that copper is a notable trace element that is crucial for biological processes and has been shown to display pro-tumorigenic functions in cancer, particularly gliomas.
Differential gene expression, Cox regression, and least absolute shrinkage and selection operator regression were used to identify 19 copper-homeostasis-related gene signatures using TCGA lower-grade glioma and glioblastoma (GBM) cohorts. The GLASS Consortium dataset was used as an independent validation cohort. Enrichment analysis revealed the involvement of the signature in various cancer-related pathways and biological processes. Using this CHRG signature, a risk score model and a nomogram were developed to predict survival in glioma patients.
Our prognostic CHRG signature stratified patients into high- and low-risk groups, demonstrating robust predictive performance. High-risk groups showed poorer survival outcomes. The nomogram model integrating CHRG signature and clinical features accurately predicted 1-, 3-, and 5-year survival rates in both training and test sets.
The identified 19-gene CHRG signature holds promise as a prognostic tool, enabling accurate risk stratification and survival prediction in glioma patients. Integrating this signature with clinical characteristics enhances prognostic accuracy, underscoring its potential clinical utility in optimizing therapeutic strategies and patient care in glioma management.
成人型弥漫性胶质瘤占中枢神经系统原发性肿瘤的近四分之一,包括星形细胞瘤、少突胶质细胞瘤和胶质母细胞瘤。组织病理学肿瘤分级和分子特征对患者生存有明显影响。尽管治疗取得了进展,但复发性胶质瘤患者的临床结局非常差,需要改进风险分层以确定治疗干预措施。各种研究表明,铜是一种重要的微量元素,对生物过程至关重要,并且已被证明在癌症,特别是胶质瘤中发挥促肿瘤发生的作用。
使用差异基因表达、Cox回归以及最小绝对收缩和选择算子回归,利用TCGA低级别胶质瘤和胶质母细胞瘤(GBM)队列鉴定了19个与铜稳态相关的基因特征。GLASS联盟数据集用作独立验证队列。富集分析揭示了该特征参与各种癌症相关途径和生物过程。利用这个CHRG特征,开发了一个风险评分模型和一个列线图来预测胶质瘤患者的生存情况。
我们的预后CHRG特征将患者分为高风险和低风险组,显示出强大的预测性能。高风险组的生存结局较差。整合CHRG特征和临床特征的列线图模型在训练集和测试集中均准确预测了1年、3年和5年生存率。
所鉴定的19基因CHRG特征有望作为一种预后工具,能够在胶质瘤患者中进行准确的风险分层和生存预测。将该特征与临床特征相结合可提高预后准确性,强调了其在优化胶质瘤治疗策略和患者护理方面的潜在临床应用价值。