Identification of SUMOylation biomarkers in glioblastoma based on transcriptome and Mendelian randomization combined with single-cell RNA-seq analysis

Aberrant SUMOylation has been associated with cancer, neurodegenerative diseases, and infections, but its exact role in glioblastoma (GBM) remains unknown. This study aimed to uncover this link and identify novel biomarkers for GBM treatment. NPC2, SPI1, and LRRC25 were identified as prognostic biomarkers for GBM outcomes. MR analysis showed that NPC2 and LRRC25 increased GBM risk, while SPI1 had a protective effect. A nomogram effectively predicted GBM prognosis. These biomarkers were enriched in pathways such as allograft rejection, inflammatory response, and IL6-JAK-STAT3 signaling. Significant immune differences were found between GBM and normal groups, with NPC2 correlating with M2 macrophages and activated NK cells, and SPI1 with HAVCR2. These biomarkers were expressed in actively propagating macrophages, macrophages, and dendritic cells, and were consistently up regulated in GBM datasets. These findings suggest that NPC2, SPI1, and LRRC25 are SUMOylation-related biomarkers for GBM, offering potential novel therapeutic targets.