Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitors
Background Metabolomics has the characteristics of terminal effects and reflects the physiological state of biological diseases more directly. Several current biomarkers of multiple omics were revealed to be associated with immune-related adverse events (irAEs) occurrence. However, there is a lack o...
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BMJ Publishing Group
2024-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/7/e009399.full |
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| author | Juan Chen Jun-yan Liu Fan Yang Ting Zou Zhan Wang Jia-Si Liu Lei She Xiang-Ping Li Zhaoqian Liu |
| author_facet | Juan Chen Jun-yan Liu Fan Yang Ting Zou Zhan Wang Jia-Si Liu Lei She Xiang-Ping Li Zhaoqian Liu |
| author_sort | Juan Chen |
| collection | DOAJ |
| description | Background Metabolomics has the characteristics of terminal effects and reflects the physiological state of biological diseases more directly. Several current biomarkers of multiple omics were revealed to be associated with immune-related adverse events (irAEs) occurrence. However, there is a lack of reliable metabolic biomarkers to predict irAEs. This study aims to explore the potential metabolic biomarkers to predict risk of irAEs and to investigate the association of plasma metabolites level with survival in patients with lung cancer receiving PD-1/PD-L1 inhibitor treatment.Methods The study collected 170 plasmas of 85 patients with lung cancer who received immune checkpoint inhibitors (ICIs) treatment. 58 plasma samples of 29 patients with irAEs were collected before ICIs treatment and at the onset of irAEs. 112 plasma samples of 56 patients who did not develop irAEs were collected before ICIs treatment and plasma matched by treatment cycles to onset of irAEs patients. Untargeted metabolomics analysis was used to identify the differential metabolites before initiating ICIs treatment and during the process that development of irAEs. Kaplan-Meier curves analysis was used to detect the associations of plasma metabolites level with survival of patients with lung cancer.Results A total of 24 differential metabolites were identified to predict the occurrence of irAEs. Baseline acylcarnitines and steroids levels are significantly higher in patients with irAEs, and the model of eight acylcarnitine and six steroid metabolites baseline level predicts irAEs occurrence with area under the curve of 0.91. Patients with lower concentration of baseline decenoylcarnitine(AcCa(10:1) 2, decenoylcarnitine(AcCa(10:1) 3 and hexanoylcarnitine(AcCa(6:0) in plasma would have better overall survival (OS). Moreover, 52 differential metabolites were identified related to irAEs during ICIs treatment, dehydroepiandrosterone sulfate, corticoserone, cortisol, thyroxine and sphinganine 1-phaosphate were significantly decreased in irAEs group while oxoglutaric acid and taurocholic acid were significantly increased in irAEs group.Conclusions High levels of acylcarnitines and steroid hormone metabolites might be risk factor to development of irAEs, and levels of decenoylcarnitine (AcCa(10:1) 2, decenoylcarnitine (AcCa(10:1) 3 and hexanoylcarnitine (AcCa(6:0) could be used to predict OS for patients with lung cancer received ICIs treatment. |
| format | Article |
| id | doaj-art-e859f974f18143f583d04df53a0dd5ed |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-e859f974f18143f583d04df53a0dd5ed2025-08-20T03:00:21ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-07-0112710.1136/jitc-2024-009399Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitorsJuan Chen0Jun-yan Liu1Fan Yang2Ting Zou3Zhan Wang4Jia-Si Liu5Lei She6Xiang-Ping Li7Zhaoqian Liu8Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, People`s Republic of ChinaDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People`s Republic of ChinaNational Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaNational Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, Hunan, People`s Republic of China4 Department of Hepatopancreatobiliary Surgery, the Affiliated Hospital of Qinghai University, Qinghai University, Xining, Qinghai, ChinaDepartment of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People`s Republic of ChinaDepartment of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People`s Republic of ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, People`s Republic of ChinaDepartment of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People`s Republic of ChinaBackground Metabolomics has the characteristics of terminal effects and reflects the physiological state of biological diseases more directly. Several current biomarkers of multiple omics were revealed to be associated with immune-related adverse events (irAEs) occurrence. However, there is a lack of reliable metabolic biomarkers to predict irAEs. This study aims to explore the potential metabolic biomarkers to predict risk of irAEs and to investigate the association of plasma metabolites level with survival in patients with lung cancer receiving PD-1/PD-L1 inhibitor treatment.Methods The study collected 170 plasmas of 85 patients with lung cancer who received immune checkpoint inhibitors (ICIs) treatment. 58 plasma samples of 29 patients with irAEs were collected before ICIs treatment and at the onset of irAEs. 112 plasma samples of 56 patients who did not develop irAEs were collected before ICIs treatment and plasma matched by treatment cycles to onset of irAEs patients. Untargeted metabolomics analysis was used to identify the differential metabolites before initiating ICIs treatment and during the process that development of irAEs. Kaplan-Meier curves analysis was used to detect the associations of plasma metabolites level with survival of patients with lung cancer.Results A total of 24 differential metabolites were identified to predict the occurrence of irAEs. Baseline acylcarnitines and steroids levels are significantly higher in patients with irAEs, and the model of eight acylcarnitine and six steroid metabolites baseline level predicts irAEs occurrence with area under the curve of 0.91. Patients with lower concentration of baseline decenoylcarnitine(AcCa(10:1) 2, decenoylcarnitine(AcCa(10:1) 3 and hexanoylcarnitine(AcCa(6:0) in plasma would have better overall survival (OS). Moreover, 52 differential metabolites were identified related to irAEs during ICIs treatment, dehydroepiandrosterone sulfate, corticoserone, cortisol, thyroxine and sphinganine 1-phaosphate were significantly decreased in irAEs group while oxoglutaric acid and taurocholic acid were significantly increased in irAEs group.Conclusions High levels of acylcarnitines and steroid hormone metabolites might be risk factor to development of irAEs, and levels of decenoylcarnitine (AcCa(10:1) 2, decenoylcarnitine (AcCa(10:1) 3 and hexanoylcarnitine (AcCa(6:0) could be used to predict OS for patients with lung cancer received ICIs treatment.https://jitc.bmj.com/content/12/7/e009399.full |
| spellingShingle | Juan Chen Jun-yan Liu Fan Yang Ting Zou Zhan Wang Jia-Si Liu Lei She Xiang-Ping Li Zhaoqian Liu Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitors Journal for ImmunoTherapy of Cancer |
| title | Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitors |
| title_full | Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitors |
| title_fullStr | Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitors |
| title_full_unstemmed | Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitors |
| title_short | Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitors |
| title_sort | plasma metabolomics of immune related adverse events for patients with lung cancer treated with pd 1 pd l1 inhibitors |
| url | https://jitc.bmj.com/content/12/7/e009399.full |
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