The Utility of Nicotinamide N-Methyltransferase as a Potential Biomarker to Predict the Oncological Outcomes for Urological Cancers: An Update

Abstract

Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation reaction of nicotinamide, using S-adenosyl-L-methionine as the methyl donor. Enzyme overexpression has been described in many non-neoplastic diseases, as well as in a wide range of solid malignancies. This review aims to report and discuss evidence available in scientific literature, dealing with NNMT expression and the potential involvement in main urologic neoplasms, namely, renal, bladder and prostate cancers. Data illustrated in the cited studies clearly demonstrated NNMT upregulation (pathological vs. normal tissue) in association with these aforementioned tumors. In addition to this, enzyme levels were also found to correlate with key prognostic parameters and patient survival. Interestingly, NNMT overexpression also emerged in peripheral body fluids, such as blood and urine, thus leading to candidate the enzyme as promising biomarker for the early and non-invasive detection of these cancers. Examined results undoubtedly showed NNMT as having the capacity to promote cell proliferation, migration and invasiveness, as well as its potential participation in fundamental events highlighting cancer progression, metastasis and resistance to chemo- and radiotherapy. In the light of this evidence, it is reasonable to attribute to NNMT a promising role as a potential biomarker for the diagnosis and prognosis of urologic neoplasms, as well as a molecular target for effective anti-cancer treatment.

Hypomethylation of CLDN4 Gene Promoter Is Associated with Malignant Phenotype in Urinary Bladder Cancer

“…BUC is associated with abnormal DNA methylation, and disruption of the methylation pattern establishment mechanism may result in deregulation of DNA methyltransferases and demethylases and altered metabolism of methyl groups [ 37 ]. In BUCs, several methyltransferases are upregulated [ 38 , 39 , 40 ]; their enhanced activity may result in depletion of methyl donors, thus potentially inducing an hypomethylation of gene promoters.…”

Biomarkers of Bladder Cancer: Cell-Free DNA, Epigenetic Modifications and Non-Coding RNAs

“…Recently in cancer research, overexpression of enzymes has been found in various cancer types [ 134 ]. In BC, overexpression of nicotinamide N-methyltransferase (NNMT) in urine is a novel biomarker studied in association with progression and aggressiveness [ 135 ].…”

Detection of Urinary Molecular Marker Test in Urothelial Cell Carcinoma: A Review of Methods and Accuracy

“…It seems arbitrary to compare the results of this study with those of the current specialized literature when the cut-off values as well as the types of urine sampling methods investigated were different (voided urine, urothelial brushing, urothelial washing, and passively collected urine). Comparing the analyses for the above-mentioned biomarkers, no difference in sensitivity or specificity was found between the NMP22 test kit (cut-o >10 U/mL) and the BTA Stat in different stages and tumor grades [ 18 ].…”

“…There is a proposed test for urological neoplasms that detects Nicotinamide N-Methyltransferase (NNMT) in exfoliated cells extracted from urine samples obtained from Bca patients and healthy individuals. A significant difference was observed between urine samples from patients suffering from Bca and those from controls [ 18 ]. There is no doubt that further and detailed research is needed on this marker.…”