To investigate the expression of N-acetyltransferase 1 (NAT1) in colon cancer (CC) and its relation with prognosis of patients.

The expression of NAT1 mRNA in 33 tumors was analyzed based on TIMER database, and immunohistochemical method was used to verify the expression of NAT1 protein in CC using HPA database. The correlation between NAT1 mRNA expression and CC clinical pathology parameters overall survival (OS) was studied using TCGA and GEO databases. GSEA was applied to predict the potential signaling pathways. The CIBERSORT algorithm was used to investigate the correlation between the immune cells and NAT1.

The TIMER database showed that NAT1 mRNA expression was significantly down-regulated in 13 tumors. Based on TCGA database, GSE44076、GSE44861 and GSE73360, the expression level of NAT1 in CC tissues was significantly lower than that of normal tissues and adjacent normal tissues (all P＜0.01). The immunohistochemical results of the HPA database suggested that NAT1 protein was lowly expressed in CC tissues. The TCGA database showed that NAT1 mRNA expression was significantly correlated with, N stage, M stage and TNM tumor stage (all P＜0.05). the OS of patients with high expression of NAT1 were significantly better than those of patients with low expression (all P＜0.05). Univariate and multivariate Cox analysis showed that NAT1 was risk factor affecting OS of CC patients and the nomogram was constructed. Tumor tissues of 35 patients with colon cancer were selected as the colon cancer group, and the adjacent normal tissues were selected as the control group. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression level of NAT1, which is consistent with predictions. GSEA showed that the high expressions of NAT1 up-regulated ascorbate and aldarate metabolism, pentose and glucuronate interconversions, starch and sucrose metabolism, porphyrin and chlorophyll metabolism, retinol metabolism, drug metabolism-other enzymes; while down-regulated glycosaminoglycan biosynthesis pathway, hedgehog signaling pathway, basal cell carcinoma, ECM receptor interaction, neuroactive ligand-receptor interaction, Wnt signaling pathway. Differences in immune cell infiltration between the high NAT1 group and the low NAT1 group were compared between the two groups. Differences in the abundance of different white blood cell subtypes showed that B cells naive, T cells CD4 memory resting, dendritic cells resting and dendritic cells activated were significantly increased in the high NAT1 group, while M0 macrophages were significantly decreased (P＜0.05).

The expression of NAT1 mRNA is down-regulated in CC. The low expression of NAT1 suggests poor prognosis and may serve as a therapy target in CC.