Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often metastasizes to the lungs. The implications of lysine lactylation (Kla), a recently identified histone post‐translational modification (PTM), in the pathology of HCC remain unclear. Here, we report the first proteomic survey of this specific modification in HCC (with no metastasis during 3 years of follow‐up), normal liver tissues, and lung metastasis samples of HCC. Of the 2045 modification sites detected on 960 proteins, 1438 sites on 772 proteins contained quantitative information. Subsequently, we analyzed the differentially modified proteins among the different groups. Differentially lactylated proteins were found to be involved in several biological processes, including‐but not limited to‐amino acid metabolism, ribosomal protein synthesis, and fatty acid metabolism. In addition, we identified numerous highly valuable lactate‐modified proteins from the literature. Among them, we verified the lactate modification levels of the following two tumor‐related proteins and obtained similar results: USP14 and ABCF1. These two modified proteins will be further investigated in our future studies. This paper is the first report on the lactylome of HCC and it provides a reliable foundation for further research on Kla in HCC.