STEAP3 can predict the prognosis and shape the tumor microenvironment of clear cell renal cell carcinoma.

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system characterized by poor prognosis and difficult treatment. It has been reported that iron metabolism dysregulation is a common phenomenon in ccRCC and is closely related to the process of ccRCC. But still now, the exact function and underlying mechanisms of iron metabolism dysregulation in ccRCC have not been fully elucidated. In this study, we comprehensively investigated the prognostic value and potential role of STEAP3 (an iron metabolism-related gene) in ccRCC. STEAP3 is significantly up-regulated in ccRCC. High STEAP3 expression is associated with gender, hemoglobin level, pathological grade, tumor stage and significantly predicts an unfavorable prognosis of ccRCC patients. Functional enrichment analysis and evaluation of the tumor microenvironment indicated that STEAP3 was involved in the remodeling of tumor extracellular matrix and the shaping of an immune-suppressive tumor microenvironment to promote tumor metastasis and evade immune killing. Besides, the expression of STEAP3 is also associated with the expression of various immune checkpoint molecules and the IC50 of targeted drugs. Finally, we verified STEAP3 by RT-qPCR and IHC staining. In conclusion, we found that STEAP3 can serve as a candidate prognostic biomarker for ccRCC, and targeting STEAP3 and its biological processes may provide new references for the individualized treatment of ccRCC.