High stromal nicotinamide N-methyltransferase (NNMT) indicates poor prognosis in colorectal cancer.

PURPOSE: Nicotinamide n-methyltransferase (NNMT) has good biochemical activity and epigenetic regulation, and has been reported as a major metabolic regulator of cancer. The goal of this study was to investigate the significance of stromal NNMT expression in colorectal cancer (CRC). PATIENTS AND METHODS: Stromal expression of NNMT in primary CRC, metastasis CRC, and their non-cancerous tissues from 1088 CRC patients was examined by immunohistochemistry. The associations between stromal NNMT expression and survival outcomes in 967 patients with stage I-III CRC were further evaluated with Kaplan-Meier curve and Cox model analyses. RESULTS: NNMT expression was mainly sourced from stromal compartments and also elevated in CRC. Patients with high stromal NNMT (IHC-score ≥ 106) have a worse survival than those patients with low stromal NNMT. In multiple Cox analyses, high expression of stromal NNMT remained as an independent risk factor in CRC for disease-free survival with a hazard ratio (HR) of 1.415 (95% confidence interval [CI], 1.015-1.972) and disease-specific survival with a HR of 5.004 (95% CI, 2.301-10.883). In addition, high stromal NNMT expression in CRC also indicates the poor survival outcomes in patients with early stage CRC (stage I and II) and in patients who undergo chemotherapy. CONCLUSION: NNMT is mainly located in CRC stromal compartment. High stromal NNMT expression predicts an unfavorable postoperative prognosis.