EPB41L3作为一种预后生物标志物，可抑制细胞恶性肿瘤并与胶质瘤中的免疫微环境相关。

EPB41L3 as a prognostic biomarker suppressing cellular malignancy and correlating with the immune microenvironment in glioma.

作者信息

Liu Xiang, Liu Yi, Du Kunpeng, Wang Changqian, Zhang Yangfeng, Li Lilin, Wang Duanyu, Chen Ling, Nov Pengkhun, Li Jiqiang, Zeng Rong

机构信息

Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.

出版信息

Biochem Biophys Res Commun. 2025 Sep 8;778:152305. doi: 10.1016/j.bbrc.2025.152305. Epub 2025 Jul 9.

DOI:10.1016/j.bbrc.2025.152305

PMID:40674816

Abstract

BACKGROUND

Glioma, the most common primary tumour of the nervous system. The prognosis of glioma often depends on WHO grade. EPB41L3 (4.1B/Dal-1) is involved in the development and progression of multiple tumours. However, the role of EPB41L3 in glioma remains to be elucidated.

METHODS

EPB41L3 mRNA expression in glioma was analysed in multiple datasets. Overall survival (OS) and progression-free interval (PFI) were analysed in patients who were divided into high and low EPB41L3 expression groups. The correlation between EPB41L3 expression and methylation was analysed and subsequently validated in glioma cells. Whether EPB41L3 impacts the tumour immune microenvironment (TIME) was investigated by evaluating its association with immune function, immune cells, and immune checkpoints. Additionally, EPB41L3's tumor-suppressive role was confirmed through functional assays including cell proliferation, invasion, flow cytometry-based cell cycle, and apoptosis analysis.

RESULTS

EPB41L3 expression was lower in glioma than in normal tissues. The immunohistochemical results showed that EPB41L3 expression gradually decreased with increasing WHO grade. Patients with glioma had longer OS and PFI in the high EPB41L3 expression group. EPB41L3 expression was negatively correlated with methylation, and most methylation sites were associated with poor OS in glioma. In addition, EPB41L3 was associated with various immune functions, immune cells, and immune checkpoints. EPB41L3-overexpressing cells were generated by lentiviral transduction. CCK-8, colony formation, Transwell, and scratch assays showed that EPB41L3 inhibited glioma cell proliferation and migration. EPB41L3 inhibits glioma mainly through apoptosis induction. Cell cycle and apoptosis results showed that EPB41L3 could inhibit glioma through apoptosis.

CONCLUSION

EPB41L3 expression is lower and the methylation level is higher in glioma, which not only play roles in tumour suppression but also are related to prognosis and the tumour immune microenvironment. EPB41L3 can be used as a prognostic and therapeutic biomarker for glioma.

摘要

背景

胶质瘤是神经系统最常见的原发性肿瘤。胶质瘤的预后通常取决于世界卫生组织（WHO）分级。EPB41L3（4.1B/Dal-1）参与多种肿瘤的发生和发展。然而，EPB41L3在胶质瘤中的作用仍有待阐明。

方法

在多个数据集中分析胶质瘤中EPB41L3 mRNA的表达。将患者分为EPB41L3高表达组和低表达组，分析总生存期（OS）和无进展生存期（PFI）。分析EPB41L3表达与甲基化之间的相关性，并随后在胶质瘤细胞中进行验证。通过评估EPB41L3与免疫功能、免疫细胞和免疫检查点的关联，研究其是否影响肿瘤免疫微环境（TIME）。此外，通过细胞增殖、侵袭、基于流式细胞术的细胞周期和凋亡分析等功能实验，证实了EPB41L3的肿瘤抑制作用。

结果

胶质瘤中EPB41L3的表达低于正常组织。免疫组化结果显示，随着WHO分级的增加，EPB41L3表达逐渐降低。EPB41L3高表达组的胶质瘤患者具有更长的OS和PFI。EPB41L3表达与甲基化呈负相关，并且大多数甲基化位点与胶质瘤患者的不良OS相关。此外，EPB41L3与多种免疫功能、免疫细胞和免疫检查点相关。通过慢病毒转导产生了过表达EPB41L3的细胞。CCK-8、集落形成、Transwell和划痕实验表明，EPB41L3抑制胶质瘤细胞的增殖和迁移。EPB41L3主要通过诱导凋亡抑制胶质瘤。细胞周期和凋亡结果表明，EPB41L3可通过凋亡抑制胶质瘤。