Furthermore, integrated research using bioinformatics and cell biology can provide new insights into prognostic biomarkers in clear cell renal cell carcinoma (ccRCC)15, 16, particularly in relation to metabolism-related genes17.Previous experimental data have reported that HMGCS2 participates in various disease processes or the maintenance of body homeostasis by limiting ketone body production, including diabetic nephropathy, colorectal cancer, hepatocellular carcinoma, intestinal stem cell homeostasis, and mitochondrial metabolic reprogramming2, 18–21. Here, HMGCS2 is linked to nonpapillary renal cell carcinoma.