Abstract
Enolase 2 (ENO2) has increasingly been documented in multiple cancers in recent years. However, the role of ENO2 in clear cell renal carcinoma (ccRCC) has not been fully explored. In the present study, open-access data were downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) databases. All statistical analyses were performed in R and GraphPad Prism 8 softwares. Results showed that ENO2 was overexpressed in ccRCC tissues and cell lines and correlated with worse clinical features and prognosis. In vitro experiments indicated that the inhibition of ENO2 could hamper the malignant behaviors of ccRCC cells. Gene Set Enrichment Analysis showed that epithelial-mesenchymal transition, KRAS signaling, inflammatory response, angiogenesis, hypoxia, and WNT/β-catenin pathways were upregulated in the ENO2 high-expression group; whereas adipogenesis, DNA repair, and androgen response pathways were downregulated. Immune infiltration analysis indicated that patients with high ENO2 levels might have higher M2 macrophages and lower γβ T cells in the tumor microenvironment, which may account to some extent for the worse prognosis of ENO2. Moreover, it was found that patients with low and high ENO2 expression might be more sensitive to PD-1 therapy and CTLA-4 therapy, respectively. In addition, patients with high ENO2 expression showed lower sensitivity to common chemotherapy drugs for ccRCC, including axitinib, cisplatin, gemcitabine, pazopanib, sunitinib, and temsirolimus. Overall, these results suggest that ENO2 is a potential prognosis biomarker of ccRCC and could affect the malignant biological behavior of cancer cells, highlighting its value as a potential therapeutic target.