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ELF4是一种预后生物标志物,与胶质瘤中的免疫浸润相关。

ELF4 was a prognostic biomarker and related to immune infiltrates in glioma.

作者信息

Zhuang Zhongwei, Zhang Chunyu, Tan Yinqiu, Zhang Jing, Zhong Chunlong

机构信息

Department of Neurosurgery, Shanghai East Hospital, Nanjing Medical University, Nanjing, China.

Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

J Cancer. 2024 Aug 6;15(15):5101-5117. doi: 10.7150/jca.96886. eCollection 2024.

Abstract

ELF4 (E74-like factor 4) is a transcription factor, dysregulation of which has been associated with carcinogenesis and cancer development. Nevertheless, the precise role of ELF4 in glioma pathology and its impact on clinical outcomes remains to be investigated. In the present research, comprehensive analyses demonstrated that elevated expression of ELF4 in glioma tissues correlates with malignant phenotypes and adverse clinical outcomes. Multivariate Cox regression analysis determined that ELF4 expression could serve as a reliable predictor of glioma outcomes. (CGGA, hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.09-1.34, p<0.001; TCGA, HR: 1.19, 95%CI: 1.01-1.41, p=0.043; and Gravendeel, HR: 1.44, 95%CI: 1.15-1.80, p=0.002). Knockdown of ELF4 reduced the cell viability and migration capacity of glioma cells . In addition to the tumor invasive role, enrichment analysis revealed the overexpressed ELF4 was involved in the immune regulation, characterized by the elevated activity of Il6/Jak/Stat3 signaling, interferon alpha (IFN-α) response, and IL2/Stat5 signaling. Single-cell RNA sequencing (scRNA)-seq and spatial transcriptome (ST)-seq analyses revealed that ELF4 could induce reprogramming of tumor-associated monocytes/macrophages (TAMMs). Molecular docking analysis revealed ELF4 might be targeted by drugs/compounds, including Veliparib (ABT-888), Motesanib (AMG 706), and EHT 1864. Genomic analysis revealed that, in LGG, in the low ELF4 expression subgroup, IDH1 demonstrated a higher mutation rate, and TP53 and ATRX Chromatin Remodeler (ATRX) displayed the lower mutation rates, than the high ELF4 expression group. Our research suggests that ELF4 may contribute to the prognostic assessment of glioma and personalized medicine.

摘要

ELF4(E74样因子4)是一种转录因子,其失调与肿瘤发生和癌症发展有关。然而,ELF4在胶质瘤病理中的精确作用及其对临床结果的影响仍有待研究。在本研究中,综合分析表明,胶质瘤组织中ELF4表达升高与恶性表型和不良临床结果相关。多变量Cox回归分析确定ELF4表达可作为胶质瘤预后的可靠预测指标。(中国胶质瘤基因组图谱计划[CGGA],风险比[HR]:1.21,95%置信区间[CI]:1.09 - 1.34,p<0.001;癌症基因组图谱计划[TCGA],HR:1.19,95%CI:1.01 - 1.41,p = 0.043;以及Gravendeel队列,HR:1.44,95%CI:1.15 - 1.80,p = 0.002)。敲低ELF4可降低胶质瘤细胞的活力和迁移能力。除了肿瘤侵袭作用外,富集分析显示过表达的ELF4参与免疫调节,其特征是Il6/Jak/Stat3信号、干扰素α(IFN-α)反应和IL2/Stat5信号的活性升高。单细胞RNA测序(scRNA)-seq和空间转录组(ST)-seq分析表明,ELF4可诱导肿瘤相关单核细胞/巨噬细胞(TAMM)重编程。分子对接分析表明,ELF4可能是包括维利帕尼(ABT - 888)、莫替沙尼(AMG 706)和EHT 1864在内的药物/化合物的作用靶点。基因组分析显示,在低级别胶质瘤(LGG)中,与ELF4高表达组相比,ELF4低表达亚组中IDH1的突变率更高,而TP53和ATRX染色质重塑因子(ATRX)的突变率更低。我们的研究表明,ELF4可能有助于胶质瘤的预后评估和个性化医疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f820/11310870/c7d83e6fbef3/jcav15p5101g001.jpg

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