Hepatocellular carcinoma (HCC）是最常见的原发性肝癌类型，常转移至肺部。赖氨酸乳酸化（Kla）是一种新近识别的组蛋白翻译后修饰却其在HCC的病理学影响还不清楚。本文报道了HCC（随访3年期间未发生转移）、正常肝组织和HCC肺转移样本中这一特定修饰的第一次蛋白质组学调查。在960种蛋白质上检测到的2045个修饰位点中，772个蛋白上的1438个位点包含定量信息。随后，我们分析了不同组中的差异化修饰蛋白质。发现差异化乳酸化蛋白参与了多种生物学过程，其中包括但不限于氨基酸代谢、核糖体蛋白合成和脂肪酸代谢。此外，我们从文献中鉴定出了大量高价值的乳酸修饰蛋白质。其中，我们验证了以下两种与肿瘤相关的蛋白的乳酸修饰水平，并获得了相似的结果：USP14和ABCF1。这两种修饰蛋白将在我们未来的研究中进一步探究。本文是HCC乳酸组学的首次报告，为进一步研究HCC中Kla提供了可靠的基础。©2023 Wiley-VCH GmbH。

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.© 2023 Wiley-VCH GmbH.