AUTHOR=Shi Cheng , Xie Li-ye , Tang Yan-ping , Long Long , Li Ji-lin , Hu Bang-li , Li Ke-zhi 

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

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01097

DOI=10.3389/fgene.2019.01097

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> The <italic>N</italic>-acetyltransferase 1 (<italic>NAT1</italic>) 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 <italic>NAT1</italic> methylation in colon adenocarcinoma (COAD).</p><p><bold>Methods:</bold> Data relating to <italic>NAT1</italic> 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 <italic>NAT1</italic> between COAD and normal tissues and performed correlation analysis to assess the association between <italic>NAT1</italic> mRNA expression and methylation. Furthermore, we assessed patient survival based on CpG sites in the promoter region of <italic>NAT1</italic> and analyzed the association between the <italic>NAT1</italic> mRNA expression and CpG site methylation and clinicopathological features. An independent Gene Expression Omnibus (GEO) dataset was used to validate the results.</p><p><bold>Results:</bold> We found that the expression of <italic>NAT1</italic> mRNA was reduced in COAD compared with normal tissues and that mean methylation of the eight CpG sites in the promoter region of <italic>NAT1</italic> was higher in COAD tissues than in normal tissues. Furthermore, five CpG sites were demonstrated to be significantly negatively correlated with <italic>NAT1</italic> mRNA expression in COAD. Survival analysis indicated that <italic>NAT1</italic> mRNA expression and the cg15797286 and cg18509990 sites were associated with the overall survival of COAD patients. Combined survival analysis revealed that combinations of <italic>NAT1</italic> mRNA expression with five CpG sites were significantly associated with the overall survival of COAD patients. Both <italic>NAT1</italic> 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.</p><p><bold>Conclusions:</bold> Methylation of <italic>NAT1</italic> is associated with the development of COAD, and may serve as prognostic and treatment biomarkers for COAD.</p>