Prognostic and Therapeutic Potential of Nicotinamide N-Methyltransferase and Hypoxia Inducible Lipid Droplet Associated in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of renal cancer, characterized by profound metabolic reprogramming and lipid accumulation. Despite therapeutic advancements, reliable prognostic biomarkers remain limited. This study investigates the prognostic and functional relevance of nicotinamide N-methyltransferase (NNMT), and hypoxia inducible lipid droplet associated (HILPDA) in ccRCC. METHODS: RNA sequencing was performed on tumor and matched normal tissues from 14 ccRCC patients. Differential gene expression and pathway enrichment analyses were conducted. Receiver operating characteristic (ROC) curves were generated to assess diagnostic value. Kaplan-Meier survival analysis using The Cancer Genome Atlas data evaluated prognostic significance. NNMT knockdown experiments were conducted in ccRCC cell lines (SNU1272 and Caki-1) to assess functional relevance. RESULTS: NNMT and HILPDA were significantly upregulated in tumor tissues. Pathway analyses revealed associations with lipid metabolism and biosynthesis. ROC analysis showed high diagnostic accuracy (NNMT area under the curve [AUC], 0.923; HILPDA AUC, 0.943). Kaplan-Meier analysis demonstrated that high NNMT expression correlated with worse overall and disease-specific survival (P < 0.001), whereas HILPDA expression showed no prognostic impact. NNMT knockdown significantly reduced cell viability (P < 0.001), supporting its role in tumor progression. CONCLUSION: NNMT is a promising prognostic biomarker and potential therapeutic target in ccRCC, supported by transcriptomic, clinical, and functional validation. While the prognostic relevance of HILPDA remains inconclusive, its metabolic associations suggest potential biological significance. Further studies with larger cohorts and in vivo validation are warranted.