Institute of Neurology, The First College of Clinical Medical Science, China Three Gorges University, Department of Neurosurgery, Yichang Central People's Hospital, Yichang, 443000, China.
The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang, 443000, China.
Biochem Biophys Res Commun. 2024 Jun 4;711:149894. doi: 10.1016/j.bbrc.2024.149894. Epub 2024 Apr 5.
Low-grade glioma (LGG) has an extremely poor prognosis, and the mechanism leading to malignant development has not been determined. The aim of our study was to clarify the function and mechanism of anoikis and TIMP1 in the malignant progression of LGG.
We screened 7 anoikis-related genes from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to construct a prognostic-predicting model. The study assessed the clinical prognosis, pathological characteristics, and immune cell infiltration in both high- and low-risk groups. Additionally, the potential modulatory effects of TIMP1 on proliferation, migration, and anoikis in LGG were investigated both in vivo and in vitro.
In this study, we identified seven critical genes, namely, PTGS2, CCND1, TIMP1, PDK4, LGALS3, CDKN1A, and CDKN2A. Kaplan‒Meier (K‒M) curves demonstrated a significant correlation between clinical features and overall survival (OS), and single-cell analysis and mutation examination emphasized the heterogeneity and pivotal role of hub gene expression imbalances in LGG development. Immune cell infiltration and microenvironment analysis further elucidated the relationships between key genes and immune cells. In addition, TIMP1 promoted the malignant progression of LGG in both in vitro and in vivo models.
This study confirmed that TIMP1 promoted the malignant progression of LGG by inhibiting anoikis, providing insights into LGG pathogenesis and potential therapeutic targets.
低级别胶质瘤（LGG）预后极差，其恶性发展的机制尚未确定。本研究旨在阐明失巢凋亡和 TIMP1 在 LGG 恶性进展中的作用和机制。
我们从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）筛选了 7 个与失巢凋亡相关的基因，构建了一个预后预测模型。该研究评估了高低风险组的临床预后、病理特征和免疫细胞浸润情况。此外，还研究了 TIMP1 对 LGG 体内和体外增殖、迁移和失巢凋亡的潜在调节作用。
在这项研究中，我们鉴定了七个关键基因，即 PTGS2、CCND1、TIMP1、PDK4、LGALS3、CDKN1A 和 CDKN2A。Kaplan-Meier（K-M）曲线表明临床特征与总生存期（OS）之间存在显著相关性，单细胞分析和突变检查强调了 LGG 发展中关键基因表达失衡的异质性和关键作用。免疫细胞浸润和微环境分析进一步阐明了关键基因与免疫细胞之间的关系。此外，TIMP1 在体外和体内模型中均促进了 LGG 的恶性进展。
本研究证实 TIMP1 通过抑制失巢凋亡促进了 LGG 的恶性进展，为 LGG 的发病机制和潜在治疗靶点提供了新的见解。
