Identification of Target Genes for Novel Metabolic Strategies in the Treatment of Renal Tumors

Summary. Aim: to identify genes encoding metabolic enzymes downregulated in various types of renal tumors, aiming to develop novel metabolic therapeutic strategies for renal cancer treatment. Object and methods: twenty pairs of clear cell renal cell carcinoma (ccRCC) samples and adjacent normal tissues were analyzed. DataSet and Series files containing microarray results with gene expression data from different types of renal tumors and normal tissues were compared. Using cross-platform normalization for several reference genes, we identified downregulated genes encoding metabolic enzymes that could serve as potential targets for novel metabolic strategies in renal cancer treatment. Expression of selected genes (ALDOB, ASS1, DAO, HPD and PAH) in clear cell renal cell carcinoma was validated by real-time RT- PCR. Results: using comparative microarray analysis with cross-platform normalization across multiple reference genes, we identified seven downregulated genes in various types of renal tumors that may serve as potential targets for developing novel metabolic strategies for renal cancer treatment. The enzymes encoded by these genes are involved in amino acid metabolism (ACY1, ASS1, DAO, PAH, HPD, PIPOX) and glycolysis (ALDOB). Decreased expression of ASS1, ALDOB, DAO, HPD, and PAH in clear cell RCC was confirmed using real-time RT-PCR. Conclusion: although monotherapy has shown limited efficacy, employing diverse metabolic strategies in renal tumor treatment may yield significantly better results, particularly when combined with conventional therapies. To expand the range of antitumor targets, the identified downregulated genes could be supplemented with upregulated genes, as well as those with expression changes specific to particular tumor types. Once a comprehensive panel of potential targets is established and gene expression profiles are analyzed for individual patients, personalized metabolic strategies for renal tumor treatment can be developed.