Shatrudhan Prajapati, Shikha Yadav, Ajay Pal Singh
INTRODUCTION: The purpose of this systematic review was to assess the expression of nicotinamide N-methyltransferase (NNMT), its mechanistic value, and clinical importance in Hepatocellular Carcinoma (HCC). METHODS: A search was conducted in PubMed, Scopus, Web of Science, Google Scholar, and the Cochrane Library in accordance with PRISMA guidelines. Studies published between 2010 and 2024 that evaluated NNMT expression and its functional implications in HCC were included. Data extraction, synthesis, and qualitative analysis were performed according to standardized criteria. RESULTS: Sixty studies were included in this review. Most studies reported significantly higher NNMT overexpression in liver tumor tissue compared to non-tumor liver tissue. High NNMT levels were associated with aggressive tumor behavior, poor prognosis, and disruptions in methylation and energy metabolism. However, comparability across studies was limited due to heterogeneity in detection methods and small cohort sizes. DISCUSSION: The findings indicate that NNMT plays a crucial role in hepatocarcinogenesis by regulating methyl-donor balance and epigenetic remodeling. Although NNMT shows strong diagnostic and therapeutic potential, the current evidence is largely preclinical, high-lighting the need for multicenter validation. CONCLUSION: NNMT is a promising biomarker and therapeutic target for HCC. Future research should include quantitative assessment of NNMT expression, mechanistic validation, and clinical studies exploring NNMT inhibition strategies.