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Background  NAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.    Methods  In this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA2, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA2.    Results  Compared with normal tissues, NAT10 showed higher expression in most cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.    Conclusion  NAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.

Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?