探讨结肠癌癌组织中N-乙酰化转移酶1（NAT1）的表达及其对结肠癌患者预后的影响。

通过肿瘤免疫评估资源（TIMER）数据库分析NAT1 mRNA在33种肿瘤中的表达情况，并用人类蛋白质图谱（HPA）数据库的免疫组化结果验证NAT1蛋白在结肠癌中的表达。通过肿瘤基因图谱（TCGA）和基因表达综合（GEO）数据库获得NAT1在结肠癌中的表达数据及相关临床特征参数，分析NAT1 mRNA表达水平与结肠癌患者的临床特征和总生存期（OS）的关系，并构建预后模型。采用基因集富集分析（GSEA）预测NAT1相关的基因通路。采用CIBERSORT分析NAT1与免疫浸润的关系。

TIMER数据库分析结果显示，在13种肿瘤组织中NAT1 mRNA表达水平低于正常对照组织。TCGA数据库结果提示，结肠癌组织中NAT1 mRNA表达水平均明显低于正常对照组织或癌旁正常组织，差异均有统计学意义（均P＜0.01），并在GSE44076、GSE44861和GSE73360中得到验证。HPA数据库的免疫组化结果提示，NAT1蛋白在结肠癌组织中呈低表达。TCGA数据库分析结果提示，NAT1 mRNA表达水平与结肠癌患者的N分期、M分期和stage分期均有关（均P＜0.01）。NAT1高表达组患者OS均好于低表达组（均P＜0.05）。单因素Cox分析表明，NAT1 mRNA表达水平是影响结肠癌患者OS的危险因素（P＜0.05），并和其他危险因素构建列线图，同时使用校准曲线和ROC评估了预后模型的特异性和敏感性。选取本院确诊的35例结肠癌患者肿瘤组织作为肿瘤组，选取其癌旁正常组织作为对照组。采用实时荧光定量PCR（qRT-PCR）法检测NAT1表达水平，结果与数据库结果一致（P＜0.05）。GSEA结果提示NAT1高表达样本上调抗坏血酸和醛糖酸盐代谢、戊糖和葡萄糖醛酸的相互转化、淀粉和蔗糖代谢、卟啉和叶绿素代谢途径、视黄醇代谢、药物代谢相关酶等基因集，而下调糖胺聚糖生物合成途径、Hedgehog信号通路、基底细胞癌、ECM受体作用通路、神经活性配体-受体相互作用途径、Wnt信号通路等基因集。使用CIBERSORT计算每个样品中的免疫细胞浸润，高NAT1组免疫细胞中原始B细胞、静息记忆CD4 T细胞、静息树突状细胞、活化树突状细胞显著增加，而M0巨噬细胞显著减少（均P＜0.05）。

结肠癌中NAT1 mRNA表达水平下调，NAT1低表达提示结肠癌患者的预后差，可作为结肠癌患者治疗的潜在靶点。

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.