Translational Oncology (Mar 2025)
Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomas
- Junli Wang,
- Yu Lou,
- Xiaojun Peng,
- Mao Ye,
- Wanyue Cao,
- Jiangchao Wu,
- Zhihui Yan,
- Xiaowen Zhao,
- Yu Zhou,
- Chenlei Zheng,
- Xiaobao Wei,
- Qitai Chen,
- Chengyang Hu,
- Mingxuan Zhang,
- Lanqing Qu,
- Zeshe Chen,
- Qihan Fu,
- Weixin Wang,
- Jingsong Li,
- Qi Zhang,
- Tingbo Liang
Affiliations
- Junli Wang
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Yu Lou
- 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
- Xiaojun Peng
- Cosmos Wisdom Biotechnology Co. Ltd., Hangzhou, China
- Mao Ye
- 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
- Wanyue Cao
- 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
- Jiangchao Wu
- 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
- Zhihui Yan
- Novogene Inc., Beijing, China
- Xiaowen Zhao
- Novogene Inc., Beijing, China
- Yu Zhou
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Chenlei Zheng
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Xiaobao Wei
- 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
- Qitai Chen
- 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
- Chengyang Hu
- 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
- Mingxuan Zhang
- Zhejiang University School of Medicine, Hangzhou, China
- Lanqing Qu
- Zhejiang University School of Medicine, Hangzhou, China
- Zeshe Chen
- Zhejiang University School of Medicine, Hangzhou, China
- Qihan Fu
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Zhejiang Province, China; Department of Medical Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Weixin Wang
- Cosmos Wisdom Biotechnology Co. Ltd., Hangzhou, China
- Jingsong Li
- Research Center for Healthcare Data Science, Zhejiang Lab, Hangzhou, China
- Qi Zhang
- 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; Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Zhejiang Province, China; Zhejiang University Cancer Center, Hangzhou, China; Corresponding author at: Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.
- Tingbo Liang
- 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; Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Zhejiang Province, China; Zhejiang University Cancer Center, Hangzhou, China; Corresponding author at: Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.
- Journal volume & issue
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Vol. 53
p. 102275
Abstract
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.
