Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy

Zhong-Chen Li; Jie Wang; He-Bin Liu; Yi-Min Zheng; Jian-Hang Huang; Jia-Bin Cai; Lei Zhang; Xin Liu; Ling Du; Xue-Ting Yang; Xiao-Qiang Chai; Ying-Hua Jiang; Zheng-Gang Ren; Jian Zhou; Jia Fan; De-Cai Yu; Hui-Chuan Sun; Cheng Huang; Feng Liu

Cell Reports (Mar 2024)

Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy

Zhong-Chen Li,
Jie Wang,
He-Bin Liu,
Yi-Min Zheng,
Jian-Hang Huang,
Jia-Bin Cai,
Lei Zhang,
Xin Liu,
Ling Du,
Xue-Ting Yang,
Xiao-Qiang Chai,
Ying-Hua Jiang,
Zheng-Gang Ren,
Jian Zhou,
Jia Fan,
De-Cai Yu,
Hui-Chuan Sun,
Cheng Huang,
Feng Liu

Affiliations

Zhong-Chen Li: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China; Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
Jie Wang: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China; Minhang Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, 131 DongAn Road, Shanghai 200032, China
He-Bin Liu: Shanghai Omicsolution Co., Ltd., 28 Yuanwen Road, Shanghai 201199, China
Yi-Min Zheng: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China
Jian-Hang Huang: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China; Minhang Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, 131 DongAn Road, Shanghai 200032, China
Jia-Bin Cai: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China
Lei Zhang: Institutes of Biomedical of Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China
Xin Liu: Department of Central Laboratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Zhijiang Road, Shanghai 200071, China
Ling Du: Minhang Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, 131 DongAn Road, Shanghai 200032, China
Xue-Ting Yang: Minhang Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, 131 DongAn Road, Shanghai 200032, China
Xiao-Qiang Chai: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China
Ying-Hua Jiang: Minhang Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, 131 DongAn Road, Shanghai 200032, China
Zheng-Gang Ren: Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
Jian Zhou: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China
Jia Fan: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China
De-Cai Yu: State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China; Corresponding author
Hui-Chuan Sun: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China; Corresponding author
Cheng Huang: Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China; Corresponding author
Feng Liu: Minhang Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical of Sciences, Fudan University, 131 DongAn Road, Shanghai 200032, China; Corresponding author

Journal volume & issue: Vol. 43, no. 3
p. 113877

Abstract

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Summary: Combination therapy (lenvatinib/programmed death-1 inhibitor) is effective for treating unresectable hepatocellular carcinoma (uHCC). We reveal that responders have better overall and progression-free survival, as well as high tumor mutation burden and special somatic variants. We analyze the proteome and metabolome of 82 plasma samples from patients with hepatocellular carcinoma (HCC; n = 51) and normal controls (n = 15), revealing that individual differences outweigh treatment differences. Responders exhibit enhanced activity in the alternative/lectin complement pathway and higher levels of lysophosphatidylcholines (LysoPCs), predicting a favorable prognosis. Non-responders are enriched for immunoglobulins, predicting worse outcomes. Compared to normal controls, HCC plasma proteins show acute inflammatory response and platelet activation, while LysoPCs decrease. Combination therapy increases LysoPCs/phosphocholines in responders. Logistic regression/random forest models using metabolomic features achieve good performance in the prediction of responders. Proteomic analysis of cancer tissues unveils molecular features that are associated with side effects in responders receiving combination therapy. In conclusion, our analysis identifies plasma features associated with uHCC responders to combination therapy.

CP: Cancer

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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