Department of Neurosurgery, The Affliated Chuzhou Hospital of Anhui Medical University, The First People's Hospital of Chuzhou, Chuzhou 239000, China.
Department of Neurosurgery, The Affliated Chuzhou Hospital of Anhui Medical University, The First People's Hospital of Chuzhou, Chuzhou 239000, China.
Int Immunopharmacol. 2024 Dec 5;142(Pt A):113084. doi: 10.1016/j.intimp.2024.113084. Epub 2024 Sep 6.
Apoptosis continues to be a pivotal area of investigation in glioma research. ADAP2 mediates the malignant progression of gliomas through the inhibition of apoptosis and predicts the overall survival(OS) of glioma patients based on prognostic modeling of the apoptotic gene set.
The study encompassed 686 glioma patients, with 413 allocated to the training group and 273 to the validation group. Differential expression of ADAP2 across various glioma subtypes was assessed through bioinformatics analysis and Western blotting. The correlation between ADAP2 and apoptosis was examined using Gene Set Enrichment Analysis (GSEA). Multivariate Cox regression analysis and LASSO dimension reduction analysis were employed to identify apoptosis-related genes with prognostic significance in glioma patients and to construct a nomogram. Biological functions and mechanisms associated with risk scores were explored via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA analyses, with validation through Western blotting, flow cytometry, and AM/PI staining.
ADAP2 was found to be enriched in more aggressive glioma subtypes and was closely linked to glioma cell apoptosis, modulating this process via the NF-κB and P53 signaling pathway. A nomogram for OS in glioma patients was constructed using thirteen apoptosis-related genes. Additionally, ROC curves, calibration curves, and C-indices confirmed the robust applicability of the nomogram.
ADAP2 functions as a prognostic biomarker for glioma patients, regulating glioma cell apoptosis through the NF-κB and P53 signaling pathway. Moreover, prognostic models based on apoptosis-related genes can accurately predict OS for glioma patients at 1, 2, 3, 5, and 10 years.
细胞凋亡持续成为神经胶质瘤研究中的一个重要领域。衔接蛋白 2(ADAP2)通过抑制细胞凋亡来介导神经胶质瘤的恶性进展,并基于凋亡基因集的预后模型预测神经胶质瘤患者的总生存期(OS)。
本研究纳入了 686 名神经胶质瘤患者,其中 413 名患者被分配到训练组,273 名患者被分配到验证组。通过生物信息学分析和 Western blot 检测 ADAP2 在不同神经胶质瘤亚型中的差异表达。使用基因集富集分析(GSEA)检测 ADAP2 与细胞凋亡的相关性。采用多变量 Cox 回归分析和 LASSO 降维分析,鉴定与神经胶质瘤患者预后相关的细胞凋亡相关基因,并构建列线图。通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)和 GSEA 分析探讨与风险评分相关的生物学功能和机制,并通过 Western blot、流式细胞术和 AM/PI 染色进行验证。
ADAP2 在侵袭性更强的神经胶质瘤亚型中富集,与神经胶质瘤细胞凋亡密切相关,通过 NF-κB 和 P53 信号通路调节这一过程。使用 13 个与细胞凋亡相关的基因构建了用于预测神经胶质瘤患者 OS 的列线图。此外,ROC 曲线、校准曲线和 C 指数证实了该列线图具有强大的适用性。
ADAP2 可作为神经胶质瘤患者的预后生物标志物,通过 NF-κB 和 P53 信号通路调节神经胶质瘤细胞凋亡。此外,基于与细胞凋亡相关的基因的预后模型可以准确预测神经胶质瘤患者 1、2、3、5 和 10 年的 OS。