Identification of NAA40 as a Potential Prognostic Marker for Aggressive Liver Cancer Subtypes

Liver hepatocellular carcinoma (LIHC) is a leading cause of cancer-related mortality. In this study we initially interrogated the Cancer Genome Atlas (TCGA) dataset to determine the implication of N-terminal acetyltransferases (NATs), a family of enzymes that modify the N-terminus of the majority of eukaryotic proteins, in LIHC. This examination unveiled NAA40 as the NAT family member with the most prominent upregulation and significant disease prognosis for this cancer. Focusing on this enzyme, which selectively targets histone proteins, we show that its upregulation occurs from early stages of LIHC and is not specifically correlated with any established risk factors such as viral infection, obesity or alcoholic disease. Notably, in silico analysis of TCGA and other LIHC datasets found that expression of this epigenetic enzyme is associated with high proliferating, poorly differentiating and more aggressive LIHC subtypes. In particular, NAA40 upregulation was preferentially linked to mutational or non-mutational P53 functional inactivation. Accordingly, we observed that high NAA40 expression was associated with worse survival specifically in liver cancer patients with inactivated P53. These findings define NAA40 as a NAT with potentially oncogenic functions in LIHC and uncover its prognostic value for aggressive LIHC subtypes.