STEAP3 is a prognostic biomarker that promotes glioma progression by regulating immune microenvironment and PI3K-AKT pathway

Article type: Research Article

Authors: Song, Zihan^{a; 1} | Zhao, Zijun^{b; 1} | Zhu, Siyu^a | Jin, Qianxu^c | Shi, Yunpeng^a | Zhang, Shiyang^a | Wang, Zairan^d | Wang, Yizheng^c | Zhao, Zongmao^{a; c; *}

Affiliations: [a] Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China | [b] Spine Center, Sanbo Brain Hospital, Capital Medical University, Beijing, China | [c] Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China | [d] Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

Correspondence: [*] Corresponding author: Zongmao Zhao, Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. E-mail: [email protected].

Note: [1] These authors contribute equally to this work.

Abstract: BACKGROUND: STEAP3 is a metal reductase located on the plasma membrane close to the nucleus and vesicles. Despite numerous studies indicating the involvement of STEAP3 in tumor advancement, the prognostic value of STEAP3 in glioma and the related mechanisms have not been fully investigated. METHODS: Initially, we examined the correlation between STEAP3 expression and the survival rate in various glioma datasets. To assess the prognostic capability of STEAP3 for one-year, three-year, and five-year survival, we created receiver operating characteristic (ROC) curves and nomograms. Additionally, an investigation was carried out to examine the mechanisms that contribute to the involvement of STEAP3 in gliomas, including immune and enrichment analysis. To confirm the expression of STEAP3 in LGG and GBM, tumor tissue samples were gathered, and cell experiments were conducted to explore the impacts of STEAP3. The function of STEAP3 in the tumor immune microenvironment was assessed using the M2 macrophage infiltration assay. RESULTS: We found that STEAP3 expressed differently in group with different age, tumor grade IDH and 1p19q status. The analysis of survival illustrated that glioma patients with high level of STEAP3 experienced shorter survival durations, especially for IDH-mutant astrocytoma. Cox analysis demonstrated that STEAP3 had potential to act as an independent prognostic factor for glioma. The predictive value of STEAP3 for glioma prognosis was demonstrated by ROC curves and nomogram. Immune analysis showed that STEAP3 may lead to a suppressive immune microenvironment through the control of immunosuppressive cell infiltration and Cancer-Immunity Cycle. Combining enrichment analysis and cell experiments, we discovered that STEAP3 can promote glioma progression through regulation of PI3K-AKT pathway and M2 macrophage infiltration. CONCLUSION: STEAP3 plays significant roles in the advancement of glioma by regulating immune microenvironment and PI3K-AKT pathway. It has the potential to serve as a therapy target for glioma.

Keywords: Glioma, STEAP3, prognosis, M2 macrophages, immunotherapy

DOI: 10.3233/CBM-230217

Journal: Cancer Biomarkers, vol. 38, no. 4, pp. 505-522, 2023