Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a member of the iron regulation protein family, is characterized by a high recurrence rate and a short survival time. Nevertheless, studies investigating the role of STEAP3 in glioblastoma (GB) are scarce. In this study, the prognostic value of STEAP3 was evaluated utilizing mRNA expression profiles from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases as the validation and training cohorts, respectively. Moreover, differentially expressed genes were subjected to a functional enrichment analysis. The relationship between STEAP3 and the tumor microenvironment (TME) was examined. The immunophenoscore (IPS) and tumor immune dysfunction and exclusion (TIDE) score were used to investigate response to immunotherapy. In all cohorts, GB patients with higher STEAP3 expression levels exhibited shorter overall survival (OS). Additionally, STEAP3-associated genes were primarily implicated in leukocyte migration, the JAK-STAT signaling pathway, and the cytokine-mediated signaling pathway. In the STEAP3 high-expression group, the ESTIMATEScore, ImmuneScore, StromalScore, and IPS were significantly higher. Overall, our results highlighted that STEAP3 might serve as a candidate prognostic biomarker for GB. Additionally, it might regulate the TME and influence GB metastasis.
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