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

Zhong-Chen Li¹, Jie Wang², He-Bin Liu³, Yi-Min Zheng⁴, Jian-Hang Huang², Jia-Bin Cai⁴, Lei Zhang⁵, Xin Liu⁶, Ling Du⁷, Xue-Ting Yang⁷, Xiao-Qiang Chai⁴, Ying-Hua Jiang⁷, Zheng-Gang Ren⁸, Jian Zhou⁴, Jia Fan⁴, De-Cai Yu⁹, Hui-Chuan Sun¹⁰, Cheng Huang¹¹, Feng Liu¹²

Affiliations

¹ 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.
² 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.
³ Shanghai Omicsolution Co., Ltd., 28 Yuanwen Road, Shanghai 201199, China.
⁴ 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.
⁵ Institutes of Biomedical of Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
⁶ Department of Central Laboratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Zhijiang Road, Shanghai 200071, China.
⁷ 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.
⁸ Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
⁹ 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. Electronic address: yudecai@nju.edu.cn.
¹⁰ 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. Electronic address: sun.huichuan@zs-hospital.sh.cn.
¹¹ 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. Electronic address: huang.cheng@zs-hospital.sh.cn.
¹² 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. Electronic address: liuf@fudan.edu.cn.

PMID: 38421869
DOI: 10.1016/j.celrep.2024.113877

Free article

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

Zhong-Chen Li et al. Cell Rep. 2024.

Free article

. 2024 Mar 26;43(3):113877.

doi: 10.1016/j.celrep.2024.113877. Epub 2024 Feb 27.

Authors

Affiliations

¹ 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.
² 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.
³ Shanghai Omicsolution Co., Ltd., 28 Yuanwen Road, Shanghai 201199, China.
⁴ 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.
⁵ Institutes of Biomedical of Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
⁶ Department of Central Laboratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Zhijiang Road, Shanghai 200071, China.
⁷ 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.
⁸ Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
⁹ 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. Electronic address: yudecai@nju.edu.cn.
¹⁰ 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. Electronic address: sun.huichuan@zs-hospital.sh.cn.
¹¹ 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. Electronic address: huang.cheng@zs-hospital.sh.cn.
¹² 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. Electronic address: liuf@fudan.edu.cn.

PMID: 38421869
DOI: 10.1016/j.celrep.2024.113877

Abstract

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.

Keywords: CP: Cancer; PD1; combination therapy; complement; hepatocellular carcinoma; immunotherapy; lenvatinib; lysophosphatidylcholine; machine learning; metabolomics; proteomics.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

References

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Elsevier Science
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous