A, patients with ATM Kinase Inhibitor in vitro high NNMT mRNA levels (≥ 4.40; copy number ratio) tended to have a shorter OS time (P = 0.053). Broken lines, patients with low NNMT mRNA levels (n = 72); thin lines, patients with high NNMT mRNA levels (n = 48). B, patients with high NNMT mRNA levels had a significantly shorter DFS time (P = 0.016). Broken lines, patients with low

NNMT mRNA levels (n = 72); thin lines, patients with high NNMT mRNA levels (n = 48). Table 4 Multivariate Cox regression analysis for disease-free survival Variable Hazard Ratio 95% Confidence Interval P value     Lower limit Upper limit   NNMT (low vs high) 1.89 1.17 3.07 0.0096 Tumor stage (I vs II) 1.42 0.80 2.54 0.23 Tumor stage (I vs III – IV) 2.47 1.40 4.33 0.0017 Discussion The metabolism of drugs, toxic chemicals, and hormones is important in the fields of pharmacology and endocrinology given its implication in many pathophysiological processes, such as cancer and resistance selleck kinase inhibitor to chemotherapy [21]. One of the key enzymes involved in biotransformation and drug metabolism is NNMT, which catalyzes the N-methylation of nicotinamide, pyrimidines, and other structural analogues [22, 23].

NNMT is predominantly expressed in the liver, where its activity varies with a bimodal frequency distribution, thus raising the possibility that a genetic polymorphism might play a role in regulating the enzyme activity [23]. Lower expression is observed in other organs such as the kidney, lungs, placenta, heart, and brain. Although several studies indicated differential expression of NNMT Verteporfin solubility dmso in HCC [12–15], the role of NNMT in the molecular pathogenesis of HCC has yet to be elucidated. This study focused on NNMT as a potential molecular marker responsible for determining clinicopathologic features

and the prognosis of HCC. Utilizing a large number of HCC specimens, the quantitative real-time PCR assay showed that the expression of NNMT is markedly reduced in HCCs compared to non-cancerous surrounding HDAC phosphorylation tissues, consistent with other studies [12–15]. Stratification of HCC specimens based on NNMT gene expression levels showed that NNMT expression was significantly correlated with tumor stage (P = 0.010). More importantly, the log-rank test showed that patients who expressed higher NNMT mRNA levels tended to have a shorter OS time (P = 0.053) and a significantly shorter DFS time (P = 0.016). Both NNMT expression (P = 0.0096) and high tumor stage (P = 0.0017) were found to be significant prognostic factors for DFS in a multivariate analysis. It is not clear why NNMT expression level was a significant prognostic factor for DFS but not for OS. We believe that the limited follow-up time was not the main cause of lack of correlation between NNMT and OS because the events (death or relapse) were rare after the median follow-up time of 50 months in our cohort.