STEAP3 acts as a potential prognostic biomarker correlated with M2
Macrophage infiltration and epithelial-mesenchymal transition in clear
cell renal cell carcinoma
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.