ENO2 affects the EMT process of renal cell carcinoma and participates in the regulation of the immune microenvironment

ENO2影响肾细胞癌EMT过程并参与免疫微环境的调控

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作者:Wei-Jie Chen #, Wei Yang #, Min Gong #, Yi He #, Da Xu, Jia-Xin Chen, Wen-Jin Chen, Wen-Yan Li, Yu-Qi Wang, Ke-Qin Dong, Xu Song, Xiu-Wu Pan, Xin-Gang Cui

Abstract

Clear cell renal cell carcinoma (ccRCC) is a frequent malignant tumor of the kidney which has a dismal prognosis. At present, targeted therapies and immunotherapy have achieved significant results; however, the overall survival rate of patients with ccRCC remains unacceptably poor. It is therefore necessary to find novel therapeutic and diagnostic targets for ccRCC. It has been reported that enolase 2 (ENO2) is an oncogene, although its function in the immune microenvironment and in the growth of ccRCC has yet to be fully elucidated. The present study analyzed the data of patients with ccRCC both from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and from clinical samples obtained from Third Affiliated Hospital of the Second Military Medical University to investigate the role of ENO2 in the progression of ccRCC and the correlation between ENO2 and certain clinical features. It was found that the expression of ENO2 was elevated both in patients with ccRCC retrieved from the GEO and TCGA databases and in clinical ccRCC samples obtained from Third Affiliated Hospital of the Second Military Medical University. In addition, the prognosis of patients was poorer when ENO2 was highly expressed. Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) confirmed that ENO2 participated in the regulation of various pathways in ccRCC. In vitro experiments including Cell Counting Kit‑8 cell proliferation assay, Transwell and Matrigel assays confirmed that ENO2 could promote the proliferation and migration of ccRCC cells. Furthermore, a number of immunosuppressive indicators were identified that positively correlated with ENO2 expression. In conclusion, the present study revealed that ENO2 expression promotes the proliferation, invasion and migration of ccRCC cells, and may serve as a novel predictor to evaluate prognosis and the efficacy of immune checkpoint blockade treatment for patients with ccRCC.

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