High ALG1 Expression Is Correlated With Poor Prognosis and the Immune Microenvironment in Glioma

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Glioma is the most prevalent primary tumour in the central nervous system. This study investigates ALG1 expression in glioma and its clinical significance. Using the TCGA and CGGA databases, a bioinformatics analysis examines ALG1 expression, its prognostic value, and its link to the immune microenvironment. Clinical samples are analysed using RT-qPCR, Western blotting, and immunohistochemistry/fluorescence for expression validation. Single-cell RNA sequencing (scRNA-seq) assesses ALG1's role in cell state transitions. In vitro, wound healing assays are performed after ALG1 knockdown with siRNA, and in vivo analysis uses an in situ mouse model. The pan-cancer analysis revealed that ALG1 is significantly overexpressed in varioustumours, including glioblastoma (GBM), and is linked to poor patient outcomes. A prognostic nomogram based on ALG1 levels accurately predicted 1-, 3-, and 5-year survival rates for glioma patients. In clinical samples, ALG1 was highly expressed at both mRNA and protein levels, correlating with tumour grade. Single-cell analysis showed increasing ALG1 expression from non-tumorigenic to malignant states, especially in malignant cells. ALG1 overexpression altered tumour microenvironmentsignalling, changing IL10 and CYPA pathways associated with immune suppression. Knocking down ALG1 significantly reduced glioma cell migration and downregulated EMT-related proteins like N-cadherin, β-catenin, and Vimentin. This study highlights ALG1 as a key prognostic biomarker and therapeutic target for glioma, promoting malignancy through increased cell migration, EMT modulation, and an altered immunosuppressive microenvironment.

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