Multimerin-1 modulates macrophage M2 polarization and enhances tumor cell stemness in glioblastoma.

Objectives: Glioblastoma (GBM) is one of the most aggressive brain tumors, with a poor prognosis. Brain tumor stem cells (BTSCs) play a central role in GBM progression and recurrence. This study aimed to identify key BTSC-related genes associated with GBM prognosis and explore their potential biological functions.

Methods: BTSC-related differentially expressed genes (DEGs) were identified by integrating gene expression data from public databases. Functional enrichment analyses were conducted to explore their biological relevance in GBM. The key variables associated with GBM risk and prognosis were selected using the machine learning method. Immune cell infiltration in GBM was explored through CIBERSORT. Finally, the effects of MMRN1 on cell stemness and macrophage polarization were investigated using in vitro experiments.

Results: A total of 26 upregulated BTSC-related DEGs in GBM were identified, which were enriched in immune response and pathways in cancer. MMRN1 and age were the key variables associated with GBM risk and prognosis. Higher MMRN1 expression and older age indicated a poor prognosis. MMRN1 expression was significantly elevated in GBM tissues, especially in BTSCs. Mechanistically, MMRN1 activated the TLR7/8/9-IRF5 signaling pathway and promoted M2 macrophage polarization. In vitro validation confirmed that MMRN1 overexpression enhanced GBM cell stemness and induced macrophage M2 polarization.

Discussion: MMRN1 is a critical BTSC-related biomarker that contributes to GBM progression by enhancing tumor stemness and modulating the immune microenvironment. Targeting MMRN1 May represent a promising therapeutic approach for GBM treatment.