Wang Junli, Lou Yu, Peng Xiaojun, Ye Mao, Cao Wanyue, Wu Jiangchao, Yan Zhihui, Zhao Xiaowen, Zhou Yu, Zheng Chenlei, Wei Xiaobao, Chen Qitai, Hu Chengyang, Zhang Mingxuan, Qu Lanqing, Chen Zeshe, Fu Qihan, Wang Weixin, Li Jingsong, Zhang Qi, Liang Tingbo
Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Transl Oncol. 2025 Mar;53:102275. doi: 10.1016/j.tranon.2025.102275. Epub 2025 Jan 20.
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.
肝细胞癌（HCC）是一种常见的恶性肿瘤。尽管对HCC的蛋白质组学已有深入研究，但对HCC中翻译后修饰（PTM）的情况却了解甚少。PTM本身及其相互作用可能与HCC的发生发展密切相关。在此，我们采用基于无标记定量液相色谱-串联质谱（LC-MS）的技术，对9例HCC患者的配对肿瘤组织和正常组织中的9种PTM进行了研究。我们鉴定出超过60,000个修饰位点，发现磷酸化和泛素化是肿瘤组织与正常组织之间变化最为频繁的两种PTM。在所有PTM中，丙二酰化-泛素化、磷酸化-泛素化以及琥珀酰化-丙酰化之间的相互作用最为显著。进一步分析表明，CDK2的Thr-160通过H3K27me3调控EZH2，并通过驱动PTM探索提出了一条用于HCC发展的PTPN2-STAT1-AOX1轴。总之，我们的研究提供了一个HCC中多种PTM的数据库，这可能有助于理解HCC的生物学特性并揭示药物开发的新靶点。
