A novel correlation between ATP5A1 gene expression and progression of human clear cell renal cell carcinoma identified by co-expression analysis

Clear cell renal cell carcinoma (ccRCC) is the most common solid lesion within kidneys, and its prognostic is influenced by the progression covering a complex network of gene interactions. In our study, a weighted gene co-expression network was constructed to identify gene modules associated with the progression of ccRCC (n=35). In the significant module (R(2) = −0.53), a total of 13 network hub genes were identified, and 2 of them were hub nodes in the protein-protein interaction network as well. In validation, ATP5A1 showed a higher correlation with the disease progression than any other hub gene in the hub module (P=0.001219). In the test set (n=202), ATP5A1 was also highly expressed in normal kidney than ccRCC tissues of each grade (P<0.001). Functional and pathway enrichment analysis demonstrated that ATP5A1 is overrepresented in pathway of oxidative phosphorylation, which associated with tumorigenesis and tumor progression. Gene set enrichment analysis (GSEA) also demonstrated that the gene set of ‘oxidative phosphorylation’ and metabolic pathways were enriched in ccRCC samples with ATP5A1 highly expressed (P<0.05). In conclusion, based on the co-expression analysis, ATP5A1 was validated to be associated with progression of ccRCC, probably by regulating tumor-related phosphorylation.