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.

中文翻译：

---

失巢凋亡相关基因的鉴定和验证，阐明低级别胶质瘤患者的预后和免疫机制

低级别胶质瘤（LGG）预后极差，导致恶性发展的机制尚未确定。本研究的目的是阐明失巢凋亡和TIMP1在LGG恶性进展中的功能和机制。我们从癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据库中筛选了 7 个失巢相关基因，构建了预后预测模型。该研究评估了高危组和低危组的临床预后、病理特征和免疫细胞浸润。此外，在体内和体外研究了 TIMP1 对 LGG 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) 之间存在显着相关性，单细胞分析和突变检查强调了中枢基因表达失衡在 LGG 发育中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LGG的恶性进展。这项研究证实TIMP1通过抑制失巢凋亡促进LGG的恶性进展，为了解LGG发病机制和潜在的治疗靶点提供了见解。