综合分析确定CACNG3是一种对胶质瘤患者具有预后预测价值的生物标志物。
Integrated profiling identifies CACNG3 as a prognostic biomarker for patients with glioma.
发表日期:2023 Sep 11
作者:
Enfang Shan, Yi-Nan Cao, Yang Zhang, Wen Chen, Xurui Ren, Shanjie Zhu, Xueru Xi, Shuai Mu, Mian Ma, Tongle Zhi, Xianwen Li
来源:
Brain Structure & Function
摘要:
胶质瘤是成年人中最常见的恶性原发性脑肿瘤,预后差。本研究的目的是探索与胶质瘤进展和生存结果密切相关的CACNG3作为一种预后因子,并为胶质瘤患者的诊断和治疗提供一个潜在的新分子靶点。从中国胶质瘤基因组图谱(CGGA)、癌症基因组图谱(TCGA)和基因表达纲目(GEO)的三个主要数据库中收集了CACNG3的表达以及相关的临床数据。 CGGA数据集用作训练集,而从GEO数据库获取的TCGA和GEO数据集用于验证。肿瘤组中CACNG3表达水平较低,CACNG3表达水平较低的患者整体生存期较短。此外,CACNG3的表达水平与胶质瘤分级呈负相关,这在临床样本的免疫组化结果中得到了证实。CACNG3在IDH1广型组、1p/19q非编码组和间质亚型组中的表达水平显著降低,结果表明CACNG3可作为间质分子亚型的生物标志物。此外,单变量和多因素分析验证了CACNG3在预测所有分级的胶质瘤的生存期方面的预测值。不同表达基因(DEGs)的功能注释和通路富集分析结果显示,CACNG3可能通过干扰突触传递影响胶质瘤的发展。此外,常用于胶质瘤治疗的替莫唑胺(TMZ)以剂量和时间依赖的方式增加了CACNG3的表达。因此,CACNG3在胶质瘤的发生和发展中起到了重要作用,可以作为靶向治疗的潜在生物标志物,并在将来进一步研究中进行探索。© 2023. BioMed Central Ltd., part of Springer Nature.
Gliomas are the most common malignant primary brain tumors in adults with poor prognoses. The purpose of this study is to explore CACNG3 as a prognostic factor that is closely related to the progression and survival outcome of gliomas and to provide a potential new molecular target for the diagnosis and treatment of glioma patients. CACNG3 expression and related clinical data were collected from three major databases of The Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO). The CGGA dataset was used as a training set, and TCGA and GEO datasets obtained from the GEO database were used for validation. CACNG3 was expressed at low levels in the tumor group, and the overall survival (OS) in patients with low CACNG3 expression is shorter. Furthermore, CACNG3 expression was negatively associated with glioma grades, which was confirmed in the IHC results of clinical samples. The expression level of CACNG3 in the IDH1 wide-type group, 1p/19q non-codel group, and mesenchymal subtype group was significantly reduced, and the results showed that CACNG3 could serve as a biomarker for the mesenchymal molecular subtype. In addition, the univariate and multivariate analysis verified the prognostic value of CACNG3 in predicting the OS of gliomas of all grades. The results of functional annotation and pathway enrichment analysis of differently expressed genes(DEGs), showed that CACNG3 might affect the development of glioma by interfering with synaptic transmission. Moreover, temozolomide (TMZ), commonly used in the treatment of glioma, increased CACNG3 expression in a dose and time-dependent manner. Therefore, CACNG3 plays a vital role in the occurrence and development of gliomas and can serve as a potential biomarker for targeted therapy and further investigation in the future.© 2023. BioMed Central Ltd., part of Springer Nature.