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Background:  The  N -acetyltransferase 1 ( NAT1 ) gene is downregulated in several cancers and associated with patient survival. In this study, we sought to examine the prognostic value and clinical significance of  NAT1  methylation in colon adenocarcinoma (COAD).    Methods:  Data relating to  NAT1  mRNA expression and methylation and clinicopathological features of COAD were extracted from the database of The Cancer Genome Atlas. We compared the mRNA expression and methylation of  NAT1  between COAD and normal tissues and performed correlation analysis to assess the association between  NAT1  mRNA expression and methylation. Furthermore, we assessed patient survival based on CpG sites in the promoter region of  NAT1  and analyzed the association between the  NAT1  mRNA expression and CpG site methylation and clinicopathological features. An independent Gene Expression Omnibus (GEO) dataset was used to validate the results.    Results:  We found that the expression of  NAT1  mRNA was reduced in COAD compared with normal tissues and that mean methylation of the eight CpG sites in the promoter region of  NAT1  was higher in COAD tissues than in normal tissues. Furthermore, five CpG sites were demonstrated to be significantly negatively correlated with  NAT1  mRNA expression in COAD. Survival analysis indicated that  NAT1  mRNA expression and the cg15797286 and cg18509990 sites were associated with the overall survival of COAD patients. Combined survival analysis revealed that combinations of  NAT1  mRNA expression with five CpG sites were significantly associated with the overall survival of COAD patients. Both  NAT1  mRNA and cg15797286 were associated with the T, N, and clinical stages of COAD. The GEO data indicated that cg15797286 was hypermethylated in recurrent colorectal adenomas.    Conclusions:  Methylation of  NAT1  is associated with the development of COAD, and may serve as prognostic and treatment biomarkers for COAD.

Hypermethylation of N-Acetyltransferase 1 Is a Prognostic Biomarker in Colon Adenocarcinoma