Abstract

Glioma is the most common primary central nervous system malignant tumor with high heterogeneity and poor prognosis. So far, the complex pathological process of glioma has not been fully elucidated, and there is a lack of effective biomarkers for the diagnosis and molecular targeted therapy of glioma. Using bioinformatics methods, 77 upregulated and 89 downregulated differentially expressed genes (DEGs) were detected by intersection analysis in different gene expression datasets of glioma cases from public databases. Then, GO and KEGG pathway analysis revealed that the biological functions of these upregulated DEGs were mainly focused on immune response, and the signaling pathways were mainly enriched in integrin family cell surface interactions. The overexpression of the LMAN1 gene of interest was then confirmed using the TCGA dataset and further verified by qRT-PCR in 29 clinical samples and 5 glioma cell lines. Furthermore, high expression of LMAN1 was found to be associated with higher WHO grade, IDH status, and 1p/19q co-deletion. Survival analysis showed that high expression of LMAN1 was associated with poor prognosis in glioma. Gene set enrichment analysis (GSEA) indicated that many cancer-related pathways were associated with LMAN1-high phenotype. Protein-protein interaction (PPI) analysis revealed significant interaction between LMAN1 and MCFD2, F8, and TMED10. Finally, cell experiments showed that LMAN1 knockdown significantly inhibited the proliferation, migration and invasion and promoted apoptosis in glioma cells. This study highlighted the malignant role of LMAN1 in gliomas and provided a potentially valuable biomarker for prognosis evaluation and molecular targeted therapy of glioma.

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