Integrated omics landscape of hepatocellular carcinoma suggests proteomic subtypes for precision therapy

被引：25

作者：

Xing, Xiaohua ^{[1
]}

Hu, En ^{[1
]}

Ouyang, Jiahe ^{[1
]}

Zhong, Xianyu ^{[1
]}

Wang, Fei ^{[1
]}

Liu, Kaixin ^{[1
]}

Cai, Linsheng ^{[1
]}

Zhou, Yang ^{[1
]}

Wang, Yingchao ^{[1
]}

Chen, Geng ^{[1
]}

Li, Zhenli ^{[1
]}

Wu, Liming ^{[2
]}

Liu, Xiaolong ^{[1
]}

机构：

[1] Fujian Med Univ, United Innovat Mengchao Hepatobiliary Technol, Key Lab Fujian Prov, Mengchao Hepatobiliary Hosp, Fuzhou 350025, Peoples R China

[2] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Hepatobiliary & Pancreat Surg, Hangzhou 310003, Peoples R China

来源：

CELL REPORTS MEDICINE | 2023年 / 4卷 / 12期

关键词：

PROTEOGENOMIC CHARACTERIZATION; 1ST-LINE TREATMENT; OPEN-LABEL; CANCER; SORAFENIB; REVEALS; MICROENVIRONMENT; CLASSIFICATION; BEVACIZUMAB; INFERENCE;

D O I：

10.1016/j.xcrm.2023.101315

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Patients with hepatocellular carcinoma (HCC) at the same clinical stage can have extremely different prognoses, and molecular subtyping provides an opportunity for individualized precision treatment. In this study, genomic, transcriptomic, proteomic, and phosphoproteomic profiling of primary tumor tissues and paired para-tumor tissues from HCC patients (N = 160) are integrated. Proteomic profiling identifies three HCC subtypes with different clinical prognosis, which are validated in three publicly available external validation sets. A simplified panel of nine proteins associated with metabolic reprogramming is further identified as a potential subtype-specific biomarker for clinical application. Multi-omics analysis further reveals that three proteomic subtypes have significant differences in genetic alterations, microenvironment dysregulation, kinasesubstrate regulatory networks, and therapeutic responses. Patient-derived cell-based drug tests (N = 26) show personalized responses for sorafenib in three proteomic subtypes, which can be predicted by a machine-learning response prediction model. Overall, this study provides a valuable resource for better understanding of HCC subtypes for precision clinical therapy.

引用

页数：28

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