Introduction: Renal cell carcinoma (RCC) is one of the most common malignancies globally, among which clear cell carcinoma (ccRCC) accounts for 85– 90% of all pathological types. This study aims to screen out potential genes in metastatic ccRCC so as to provide novel insights for ccRCC treatment.
Methods: GSE53757 and GSE84546 datasets in the Gene Expression Omnibus (GEO) were profiled to identify differentially expressed genes (DEGs) from ccRCC samples with or without metastasis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and the gene ontology (GO) analysis were performed to analyze pathway enrichment and functional annotation of DEGs. Protein–protein interaction (PPI) network was constructed, and survival analysis was conducted to evaluate the clinical values of the identified hub genes. In vitro loss-of-function assays were performed to explore the biological roles of these genes.
Results: The bioinformatic analysis indicated that 312 DEGs were identified, including 148 upregulated genes and 164 downregulated ones. Using PPI and Cytoscape, 10 hub genes were selected (C3 , CXCR4 , CCl4 , ACKR3 , KIF20A , CCNB2 , CDCA8 , CCL28 , S1PR5 , and CCL20 ) from DEGs which might be closely related with ccRCC metastasis. In Kaplan–Meier analysis, three potential prognostic biomarkers (KIF20A , CCNB2  and CDCA8 ) were identified. Finally, cell proliferative and invasive assays further verified that KIF20A , CCNB2  and CDCA8  were associated with the proliferation and invasion of ccRCC cells.
Conclusion: Our results demonstrated that metastatic ccRCC was partially attributed to the aberrant expression of KIF20A , CCNB2  and CDCA8 , and more personalized therapeutic approaches should be explored targeting these hub genes.
Keywords: clear cell renal cell carcinoma, hub genes, biomarkers, metastasis, differentially expressed gene