In‐depth discovery of protein lactylation in hepatocellular carcinoma

As a prevalent cancer type, hepatocellular carcinoma (HCC) accounts for a number of tumor-related deaths worldwide. Substantial efforts from various aspects, including RNA and proteins, have been devoted to understanding the mechanisms of HCC and proposing therapeutic schemes correspondingly. Within one of the important fields in cancer research - protein post-translational modifications (PTMs), recent discoveries revealed much broader landscapes of lysine lactylation (Kla) distributed in whole human proteome. Upon realizing the relation between Kla and cancers, Hong et al. (Proteomics 2023, 23, 2200432) comprehensively profiled lactylproteome in HCC tissues for the first time. All collected and processed samples were categorized into normal liver tissues, HCC without metastasis or HCC with lung metastasis tissues. As a result, 2045 Kla modification sites from 960 proteins were identified and 1438 sites from 772 proteins were quantifiably measured. Many differentially expressed Kla-proteins emerged and meant to contribute HCC formation and metastatsis. Among them, specific Kla sites from ubiquitin specific peptidase 14 (USP14) and ATP-binding cassette family 1 (ABCF1) were respectively verified as diagnostic indicators to characterize HCC and its metastasis. This work was of great significance, and made impacts in terms of further discovery of HCC rationale, as well as diagnosis of HCC status and targeted therapies.