烟酰胺-N-甲基转移酶在胃癌中高表达并与预后负相关：基于生物信息学方法

OBJECTIVE To investigate the expression of nicotinamide-N-methyltransferase (NNMT) in gastric cancer (GC) and explore its biological and clinicopathological significance. OBJECTIVE We screened the candidate genes associated with the classification and prognosis of gastric cancer by analyzing GEO, Oncomine and TCGA datasets. The molecular pathways and protein interaction network involving these candidate genes were analyzed using STRING, GSEA, David and Cytoscape software. The expressions of the candidate genes in 28 pairs of gastric cancer and adjacent tissues were detected with qRTPCR, and CCK-8 assay, clone formation assay, wound healing assay and Transwell assay were carried out to analyze the effects of modulation of NNMT expression on proliferation, invasion and migration of different gastric cancer cell lines. OBJECTIVE NNMT was highly expressed in gastric cancer tissues and was negatively correlated with the prognosis of patients with gastric cancer. Pathway analysis showed that the high expression of NNMT was associated with adhesion-related pathway molecules such as extracellular matrix receptors, cell adhesion molecules, and cytokine receptors, while its low expression was associated with base mismatch repair and riboflavin metabolism. Protein interaction analysis showed that NNMT interacted with 16 differentially expressed proteins such as AURKA and was co-expressed with TAGLN, PTRF, AKAP12 and IGF2BP2. In clinical tissue specimens, qRT-PCR results showed that the expression of NNMT mRNA was significantly higher in gastric cancer tissues than in the adjacent tissues (P < 0.05). In gastric cancer cell lines, overexpression of NNMT was found to significantly promote cell proliferation, invasion and migration, while NNMT knockdown produced obvious inhibitory effects on cell proliferation, invasion and migration. OBJECTIVE NNMT is highly expressed in gastric cancer and negatively correlated with the prognosis of gastric cancer patients. The high expression of NNMT promotes the proliferation, invasion and metastasis of gastric cancer cells, suggesting the potential of NNMT as prognostic marker of gastric cancer.