Nicotinamide N-methyltransferase:A Potential Biomarker For Worse Prognosis In Gastric Carcinoma

Background and ObjectiveIn clinical practice, cancer stage (or grade) and some biomarkers, such as carcinoembryonic antigen (CEA) and CA199, are widely used to predict the prognosis of gastric carcinoma patients. Due to the limited role of prognostic indicators for gastric carcinoma, this condition remains one of the most fatal human malignancies with a dismal prognosis. Nicotinamide N-methyltransferase (NNMT, EC.2.1.1.1), a metabolizing enzyme, is involved in the development and progression of various carcinomas. However, the prognostic and biological functions of NNMT in gastric carcinoma are not yet clear.MethodsWe firstly detected the expression of NNMT in both benign and malignant gastric tissues of patients by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Meanwhile, the prognostic and clinicopathological significance of NNMT expression was also evaluated in gastric carcinoma. To further explore the biological role of NNMT in gastric carcinoma, siRNA-mediated silence was also performed to evaluate the biological function of NNMT in gastric cancer cell line in vitro and vivo. Finally, we retrieved and analyzed the data of TCGA using the coexpression and enrichment analysis tool in cBioPortal.The list of all genes with highest expression correlation with NNMT was submitted to DAVID Bioinformatics Resources 6.7.ResultsIn the present study, NNMT was found to be overexpressed at the mRNA and protein levels in gastric carcinoma tissues compared with adjacent tissues. Importantly, the survival analysis verified that NNMT expression is an independent prognostic factor for overall survival of gastric cancer patients. Moreover, NNMT expression was related to primary tumor size, lymph node metastasis, distant metastasis, and TNM (tumor, node, and metastasis) stage. We also demonstrated that knockdown of NNMT inhibits cellular proliferation, invasion and migration in vitro and in vivo.ConclusionOverall, the results of this study suggest that NNMT is a promising prognostic predictor for gastric cancer patients and could be used as a new target for gastric cancer therapy.