Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomas.

Hepatocellular carcinoma (HCC) is a common malignant tumor. Although the proteomics of HCC is well studied, the landscape of post-translational modifications (PTMs) in HCC is poorly understood. The PTMs themselves and their crosstalk might be deeply involved in HCC development and progression. Herein, we investigated nine types of PTMs in paired tumor and normal tissues from nine patients with HCC using the label-free quantitative liquid chromatography with tandem mass spectrometry (LC-MS)-based technique. We identified >60,000 modified sites, and found that phosphorylation and ubiquitination were two most frequently changed PTMs between tumor and normal tissues. Crosstalk between malonylation-ubiquitination, phosphorylation-ubiquitination, and succinylation-propionylation were most significant among all PTMs. Further analysis revealed that Thr-160 of CDK2 regulated EZH2 via H3K27me3, and proposed a PTPN2-STAT1-AOX1 axis for HCC development through driver PTM exploration. In conclusion, our study provides a database of multiple PTMs in HCC, which might help to understand the biology of HCC and reveal novel targets for drug development.