Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy
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 t...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724002055 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zhong-Chen Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T19:42:20Z |
| format | Article |
| id | doaj.art-373fb5f605da44d19f76ab1177c0032c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T19:42:20Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-373fb5f605da44d19f76ab1177c0032c2024-02-29T05:19:06ZengElsevierCell Reports2211-12472024-03-01433113877Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapyZhong-Chen Li0Jie Wang1He-Bin Liu2Yi-Min Zheng3Jian-Hang Huang4Jia-Bin Cai5Lei Zhang6Xin Liu7Ling Du8Xue-Ting Yang9Xiao-Qiang Chai10Ying-Hua Jiang11Zheng-Gang Ren12Jian Zhou13Jia Fan14De-Cai Yu15Hui-Chuan Sun16Cheng Huang17Feng Liu18Department 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, ChinaDepartment 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, ChinaShanghai Omicsolution Co., Ltd., 28 Yuanwen Road, Shanghai 201199, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaInstitutes of Biomedical of Sciences, Fudan University, 220 Handan Road, Shanghai 200433, ChinaDepartment of Central Laboratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Zhijiang Road, Shanghai 200071, ChinaMinhang 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, ChinaMinhang 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, ChinaDepartment 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, ChinaMinhang 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, ChinaDepartment of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment 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, ChinaDepartment 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, ChinaState 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 authorDepartment 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 authorDepartment 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 authorMinhang 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724002055CP: Cancer |
| spellingShingle | 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 Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy Cell Reports CP: Cancer |
| title | Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy |
| title_full | Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy |
| title_fullStr | Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy |
| title_full_unstemmed | Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy |
| title_short | Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy |
| title_sort | proteomic and metabolomic features in patients with hcc responding to lenvatinib and anti pd1 therapy |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724002055 |
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