Identification of metabolism-associated genes and pathways involved in different stages of clear cell renal cell carcinoma.

The lack of early diagnostic markers and novel therapeutic targets for clear cell renal cell carcinoma (ccRCC) negatively affects patient prognosis. Cancer metabolism is an attractive area for the understanding of the molecular mechanism of carcinogenesis. The present study attempted to identify metabolic changes from the view of the expression of metabolism-associated genes between control samples and those of ccRCC at different disease stages. Data concerning ccRCC gene expression obtained by RNA-sequencing was obtained from The Cancer Genome Atlas and data on metabolism-associated genes were extracted using the Recon2 model. Following analysis of differential gene expression, multiple differentially expressed metabolic genes at each tumor-node-metastasis disease stage were identified, compared with control non-disease samples: Metabolic genes (305) were differentially expressed in stage I disease, 323 in stage II disease, 355 in stage III disease and 363 in stage IV disease. Following enrichment analysis for differential metabolic genes, 22 metabolic pathways were identified to be dysregulated in multiple stages of ccRCC. Abnormalities in hormone, vitamin, glucose and lipid metabolism were present in the early stages of the disease, with dysregulation to reactive oxygen species detoxification and amino acid metabolism pathways occurring with advanced disease stages, particularly to valine, leucine, and isoleucine metabolism, which was substantially dysregulated in stage IV disease. The xenobiotic metabolism pathway, associated with multiple cytochrome P450 family genes, was dysregulated in each stage of the disease. This pathway is worthy of substantial attention since it may aid understanding of drug resistance in ccRCC. The results of the present study offer information to aid further research into early diagnostic biomarkers and therapeutic targets of ccRCC.