{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:36:02Z","timestamp":1793763362004,"version":"4.6.1"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":202,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Genomics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis. This study is aimed at establishing an ubiquitin\u2010proteasome system (UPS)\u2013related prognostic model and investigating its link to immune infiltration and therapy response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      GBM datasets were obtained from public databases. Ubiquitin\u2010proteasome system\u2013related genes (UPSGs) were identified from literature. Consensus clustering defined UPS\u2010based GBM subtypes. Differentially expressed genes (DEGs) were screened, and a prognostic model was constructed using univariate Cox, least absolute shrinkage and selection operator (LASSO), and stepwise regression. The model\u2032s performance was validated using survival analysis and time\u2010dependent receiver operating characteristic (ROC) curves. Immune infiltration was assessed using single\u2010sample gene set enrichment analysis (ssGSEA), TIMER, and ESTIMATE. Drug sensitivity was assessed by correlating the half\u2010maximal inhibitory concentration (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) of candidate drugs with the risk score. Single\u2010cell RNA sequencing data were used to characterize UPSG expression across distinct cell subpopulations in GBM. For in vitro validation, key UPSGs were silenced in GBM cell lines, and cell proliferation, migration, and invasion were measured using Cell Counting Kit\u20108 (CCK\u20108), wound healing, and Transwell assays, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two UPS\u2010related GBM subtypes were identified. Six genes (\n                      <jats:italic>IGFBP6<\/jats:italic>\n                      ,\n                      <jats:italic>CTSD<\/jats:italic>\n                      ,\n                      <jats:italic>SPAG4<\/jats:italic>\n                      ,\n                      <jats:italic>ZNF560<\/jats:italic>\n                      ,\n                      <jats:italic>COL22A1<\/jats:italic>\n                      , and\n                      <jats:italic>HOXC13<\/jats:italic>\n                      ) formed the prognostic model, where high Riskscore indicated poor survival. High Riskscore correlated with greater immune infiltration, including CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and macrophages. IC\n                      <jats:sub>50<\/jats:sub>\n                      values of 24 drugs were significantly associated with Riskscore. Single\u2010cell analysis revealed seven GBM subpopulations; notably,\n                      <jats:italic>COL22A1<\/jats:italic>\n                      was enriched in MES\u2010like cells, and CTSD in macrophages.\n                      <jats:italic>IGFBP6<\/jats:italic>\n                      promoted GBM cell proliferation, migration, and invasion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study establishes a UPS\u2010based prognostic model for GBM that links immune infiltration and drug sensitivity, providing potential biomarkers and therapeutic targets for GBM.<\/jats:p>\n                  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