LYZ Gene as a Novel Therapeutic Target and Diagnostic Biomarker in Glioblastoma: Insights from Multi-Omics Analysis and Functional Validation

Immune checkpoint blockade is one of the current treatments for glioblastoma (GBM), which is still a very aggressive and treatment-resistant tumor of the central nervous system. This study focused on the LYZ gene in an attempt to find new therapeutic targets. We performed a thorough screening of differential gene expression between GBM and normal samples using many databases (TCGA, GTEx, GEO, and CGGA). Because LYZ is significantly upregulated in GBM tissues and is associated with shorter patient survival periods, we identified it as a gene of interest. LYZ's position on the exterior side of the plasma membrane and its participation in leukocyte-mediated immunity were identified by functional enrichment analysis, indicating a role in cell surface immune responses. Significant associations between LYZ expression and particular immune cell types were found using immune infiltration analysis, suggesting that LYZ may have an impact on the tumor microenvironment. Within GBM, single-cell research verified LYZ expression in macrophages and monocytes. LYZ was shown to express differently in GBM cell lines than in normal glial cells, according to cellular experimental verification. The LYZ gene's functional importance in the pathophysiology of GBM was highlighted by the dramatic reduction in cell proliferation, motility, and invasion that resulted from its knockout. These results suggest that LYZ is a viable therapeutic target and possible GBM diagnostic biomarker, which calls for more research into its mechanisms of action and potential clinical use.

免疫检查点阻断（Immune checkpoint blockade）是当前胶质母细胞瘤（glioblastoma, GBM）的治疗手段之一，而胶质母细胞瘤仍是一种极具侵袭性且治疗耐受的中枢神经系统肿瘤。本研究聚焦于LYZ基因，旨在发掘全新的治疗靶点。我们依托TCGA、GTEx、GEO与CGGA等多个数据库，全面筛查了胶质母细胞瘤与正常样本之间的差异表达基因。由于LYZ在胶质母细胞瘤组织中显著上调，且与患者更短的生存期显著相关，我们将其确定为目标研究基因。通过功能富集分析，我们明确了LYZ定位于质膜外侧，并参与白细胞介导的免疫过程，提示其在细胞表面免疫应答中发挥作用。免疫浸润分析显示，LYZ的表达与特定免疫细胞亚型存在显著关联，表明LYZ可能对肿瘤微环境产生调控作用。在胶质母细胞瘤组织内，单细胞研究证实了LYZ在巨噬细胞与单核细胞中的表达。细胞实验验证结果表明，LYZ在胶质母细胞瘤细胞系与正常胶质细胞中的表达存在显著差异。敲除LYZ基因后，细胞的增殖、迁移及侵袭能力均出现显著下降，凸显了LYZ在胶质母细胞瘤病理生理过程中的关键功能意义。上述研究结果提示，LYZ可作为潜在的治疗靶点与胶质母细胞瘤诊断生物标志物，其作用机制与临床应用潜力仍有待进一步深入探究。