代谢组学具有终末效应的特点，更直接地反映生物疾病的生理状态。目前多个组学的几种生物标志物被发现与免疫相关不良事件 (irAE) 的发生有关。然而，缺乏可靠的代谢生物标志物来预测 irAE。本研究旨在探索潜在的代谢生物标志物来预测 irAE 风险，并调查接受 PD-1/PD-L1 抑制剂治疗的肺癌患者血浆代谢物水平与生存的关系。该研究收集了 85 名患有肺癌的患者的 170 份血浆。接受免疫检查点抑制剂（ICIs）治疗的肺癌。在 ICI 治疗前和 irAE 发生时收集了 29 名 irAE 患者的 58 份血浆样本。在 ICI 治疗前收集了 56 名未发生 irAE 的患者的 112 份血浆样本，并根据治疗周期与出现 irAE 的患者进行匹配。非靶向代谢组学分析用于在开始 ICI 治疗之前和 irAE 发生过程中识别差异代谢物。采用Kaplan-Meier曲线分析检测血浆代谢物水平与肺癌患者生存的关系。共鉴定出24种差异代谢物来预测irAE的发生。 irAE 患者的基线酰基肉碱和类固醇水平显着较高，八种酰基肉碱和六种类固醇代谢物基线水平的模型预测 irAE 的发生，曲线下面积为 0.91。血浆中基线癸烯酰肉碱(AcCa(10:1) 2、癸烯酰肉碱(AcCa(10:1) 3)和己酰肉碱(AcCa(6:0))浓度较低的患者将具有更好的总生存期(OS)。此外，52种差异代谢物在ICIs治疗期间，发现与irAE相关的硫酸脱氢表雄酮、皮质酮、皮质醇、甲状腺素和1-磷酸二氢鞘氨醇显着减少，而氧化戊二酸和牛磺胆酸在irAEs组中显着增加。 高水平的酰基肉碱和类固醇激素代谢物可能是发生 irAE 的危险因素，癸烯酰肉碱 (AcCa(10:1) 2、癸烯酰肉碱 (AcCa(10:1) 3) 和己酰肉碱 (AcCa(6:0)) 水平可用于预测肺癌患者的 OS接受 ICI 治疗。© 作者（或其雇主）2024。根据 CC BY-NC 允许重复使用，禁止商业重复使用。请参阅 BMJ 发布的权利和许可。

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.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.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.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.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.