Further clustering analysis of the tumor cells identified a subcluster characterized by high expression levels of PLOD2, SAA1, C1S, and C1R. Previous studies have indeed demonstrated that PLOD2 expression can be induced by hypoxia, leading to the activation of the EGFR/AKT signaling pathway and subsequent promotion of proliferation and migration of ccRCC cells [53]. Here, C1S is linked to nonpapillary renal cell carcinoma.