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STEAP3 acts as a potential prognostic biomarker correlated with M2 Macrophage infiltration and epithelial-mesenchymal transition in clear cell renal cell carcinoma
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  • Haotian Wei,
  • Zhaochen Li,
  • Yang Zhao,
  • Shimiao Zhu,
  • Simeng Wen,
  • Changyi Quan
Haotian Wei
The Second Hospital of Tianjin Medical University
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Zhaochen Li
The Second Hospital of Tianjin Medical University
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Yang Zhao
The Second Hospital of Tianjin Medical University
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Shimiao Zhu
The Second Hospital of Tianjin Medical University
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Simeng Wen
The Second Hospital of Tianjin Medical University
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Changyi Quan
The Second Hospital of Tianjin Medical University

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Abstract

Background: The six-transmembrane epithelial antigen of the prostate 3 (STEAP3) plays an essential role in iron uptake as an iron reductase. Previous studies found that STEAP3 may play crucial roles in tumorigenesis. However, a comprehensive pan‐cancer analysis of the prognosis and immunity of STEAP3 has not yet been reported. Methods: We performed a systematic analysis of the prognosis and immunity of STEAP3 in human pan-cancer. The data analysis and visualization were completed with R and Cytoscape. STEAP3 expression in cell lines and tissues was measured in multiple ways. Functional validation experiments were performed by shRNA knockdown inA498 and 786-O cell lines. Cell proliferation and invasive ability was detected by CCK-8 assay, transwell assay and wound healing assay. Results: In most tumor tissues, STEAP3 expression was remarkably upregulated and correlated with prognosis, particularly in clear cell renal cell carcinoma (ccRCC). Furthermore, STEAP3 expression was closely correlated with immune infiltrates and may induce recruitment and polarization of M2 macrophages in ccRCC. STEAP3 may be valuable for predicting responses to immune-checkpoint blockade (ICB) therapy. In addition, enrichment analysis results indicated that STEAP3 was positively related to immune-related pathways, P53 pathways and epithelial-mesenchymal transition (EMT). Finally, we demonstrated that STEAP3 was highly expressed in ccRCC tissues and might stimulate EMT via the downregulation of CDH1 in vitro in ccRCC. Conclusion: STEAP3 might function as a prognostic biomarker and immunotherapy response predictor in various cancers. Especially in ccRCC, STEAP3 is a new prognostic biomarker and exerts tumor-promoting function via stimulating the invasion and EMT and inducing recruitment and polarization of M2 macrophages.
10 Jan 2023Submitted to Cancer Reports
12 Jan 2023Submission Checks Completed
12 Jan 2023Assigned to Editor
12 Jan 2023Review(s) Completed, Editorial Evaluation Pending
12 Jan 2023Reviewer(s) Assigned
01 Feb 2023Editorial Decision: Revise Major
27 Feb 20231st Revision Received
28 Feb 2023Assigned to Editor
28 Feb 2023Submission Checks Completed
28 Feb 2023Review(s) Completed, Editorial Evaluation Pending
15 Mar 2023Reviewer(s) Assigned
24 Mar 2023Editorial Decision: Revise Minor
30 Mar 20232nd Revision Received
30 Mar 2023Assigned to Editor
30 Mar 2023Submission Checks Completed
30 Mar 2023Review(s) Completed, Editorial Evaluation Pending
10 Apr 2023Editorial Decision: Accept