Cai Hongqing, Tian Shen, Liu Angsi, Xie Guanchao, Zhang Hongsheng, Wu Xiaogang, Wan Jinghai, Li Sai
Department of Neurosurgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China.
State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Eur J Med Res. 2025 Jan 9;30(1):17. doi: 10.1186/s40001-024-02192-w.
This study aimed to evaluate CTF1 expression in glioma, its relationship to patient prognosis and the tumor immune microenvironment, and effects on glioma phenotypes to identify a new therapeutic target for treating glioma precisely.
We initially assessed the expression of CTF1, a member of the IL-6 family, in glioma, using bioinformatics tools and publicly available databases. Furthermore, we examined the correlation between CTF1 expression and tumor prognosis, DNA methylation patterns, m6A-related genes, potential biological functions, the immune microenvironment, and genes associated with immune checkpoints. We also explored potential associations with drug sensitivity. To assess the impact on glioma cell proliferation and apoptosis, we employed various assays, including the Cell Counting Kit-8, colony formation assay, and flow cytometry.
CTF1 gene and protein expression were significantly elevated in glioma tissues, and correlated with malignancy and poor prognosis. CTF1 was an independent prognostic factor and negatively associated with DNA methylation. The involvement of CTF1 in m6A modifications contributed to glioma progression. Enrichment analysis revealed immune response pathways linked with CTF1 in glioma, including natural killer cell cytotoxicity, NOD-like receptor signaling, Toll-like receptor signaling, antigen processing, chemokine signaling, and cytokine receptor interactions. CTF1 expression correlated positively with pathways related to apoptosis, inflammation, proliferation, and epithelial-mesenchymal transition, and PI3K-AKT-mTOR signaling. Additionally, CTF1 expression was positively associated with macrophage, eosinophil, and neutrophil contents and immune checkpoint-related genes, but negatively associated with sensitivity to 14 drugs. In vitro experiments confirmed that CTF1 knockdown inhibited glioma cell proliferation and promoted apoptosis.
This study identifies CTF1 as a significant independent prognostic factor that is closely associated with the tumor immune microenvironment in glioma. Additionally, reduced expression of CTF1 suppresses the proliferation and induces apoptosis of glioma cells in vitro. Consequently, CTF1 is a potentially promising novel therapeutic target for glioma treatment.
本研究旨在评估CTF1在胶质瘤中的表达、其与患者预后及肿瘤免疫微环境的关系,以及对胶质瘤表型的影响,以确定精确治疗胶质瘤的新治疗靶点。
我们首先使用生物信息学工具和公开可用数据库评估白细胞介素-6家族成员CTF1在胶质瘤中的表达。此外,我们研究了CTF1表达与肿瘤预后、DNA甲基化模式、m6A相关基因、潜在生物学功能、免疫微环境以及与免疫检查点相关基因之间的相关性。我们还探索了与药物敏感性的潜在关联。为了评估对胶质瘤细胞增殖和凋亡的影响,我们采用了多种检测方法,包括细胞计数试剂盒-8、集落形成试验和流式细胞术。
CTF1基因和蛋白表达在胶质瘤组织中显著升高,且与恶性程度和不良预后相关。CTF1是一个独立的预后因素,与DNA甲基化呈负相关。CTF1参与m6A修饰促进了胶质瘤进展。富集分析揭示了胶质瘤中与CTF1相关的免疫反应途径,包括自然杀伤细胞细胞毒性、NOD样受体信号传导、Toll样受体信号传导、抗原加工、趋化因子信号传导和细胞因子受体相互作用。CTF1表达与凋亡、炎症、增殖和上皮-间质转化以及PI3K-AKT-mTOR信号传导相关途径呈正相关。此外,CTF1表达与巨噬细胞、嗜酸性粒细胞和中性粒细胞含量以及免疫检查点相关基因呈正相关,但与对14种药物的敏感性呈负相关。体外实验证实,敲低CTF1可抑制胶质瘤细胞增殖并促进凋亡。
本研究确定CTF1是一个重要的独立预后因素,与胶质瘤中的肿瘤免疫微环境密切相关。此外,CTF1表达降低在体外可抑制胶质瘤细胞增殖并诱导其凋亡。因此,CTF1是胶质瘤治疗中一个潜在有前景的新型治疗靶点。