文章：

早期2因子转录因子与胶质母细胞瘤贝伐珠单抗反应亚型的进展和复发相关

Early 2-Factor Transcription Factors Associated with Progression and Recurrence in Bevacizumab-Responsive Subtypes of Glioblastoma

原文发布日期：14 July 2024

DOI: 10.3390/cancers16142536

类型: Article

开放获取: 是

英文摘要：

The early 2-factor (E2F) family of transcription factors, including E2F1 through 8, plays a critical role in apoptosis, metabolism, proliferation, and angiogenesis within glioblastoma (GBM). However, the specific functions of E2F transcription factors (E2Fs) and their impact on the malignancy of Bevacizumab (BVZ)-responsive GBM subtypes remain unclear. This study used data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), European Molecular Biology Laboratory’s European Bioinformatics Institute (EMBL-EBI), and Gene Expression Omnibus (GEO) to explore the impact of eight E2F family members on the clinical characteristics of BVZ-responsive GBM subtypes and possible mechanisms of recurrence after BVZ treatment. Using machine learning algorithms, including TreeBagger and deep neural networks, we systematically predicted and validated GBM patient survival terms based on the expression profiles of E2Fs across BVZ-responsive GBM subtypes. Our bioinformatics analyses suggested that a significant increase in E2F8 post-BVZ treatment may enhance the function of angiogenesis and stem cell proliferation, implicating this factor as a candidate mechanism of GBM recurrence after treatment. In addition, BVZ treatment in unresponsive GBM patients may potentially worsen disease progression. These insights underscore that E2F family members play important roles in GBM malignancy and BVZ treatment response, highlighting their potential as prognostic biomarkers, therapeutic targets, and recommending precision BVZ treatment to individual GBM patients.

摘要翻译： 

早期2因子（E2F）转录因子家族（包括E2F1至E8）在胶质母细胞瘤（GBM）的细胞凋亡、代谢、增殖及血管生成过程中发挥关键作用。然而，E2F转录因子的具体功能及其对贝伐珠单抗（BVZ）敏感型GBM亚型恶性程度的影响尚不明确。本研究基于癌症基因组图谱（TCGA）、中国胶质瘤基因组图谱（CGGA）、欧洲分子生物学实验室-欧洲生物信息学研究所（EMBL-EBI）及基因表达综合数据库（GEO）的数据，探讨了八种E2F家族成员对BVZ敏感型GBM亚型临床特征的影响，以及BVZ治疗后肿瘤复发的潜在机制。通过运用TreeBagger和深度神经网络等机器学习算法，我们基于不同BVZ敏感型GBM亚型中E2Fs的表达谱，系统预测并验证了GBM患者的生存期。生物信息学分析表明，BVZ治疗后E2F8的显著上调可能增强血管生成与干细胞增殖功能，提示该因子可能是GBM治疗后复发的潜在机制。此外，对BVZ不敏感型GBM患者使用BVZ治疗可能加剧疾病进展。这些发现强调了E2F家族成员在GBM恶性进展及BVZ治疗反应中的重要作用，提示其可作为预后生物标志物和治疗靶点，并为个体化精准BVZ治疗提供了理论依据。

原文链接：

Early 2-Factor Transcription Factors Associated with Progression and Recurrence in Bevacizumab-Responsive Subtypes of Glioblastoma