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代谢组学分析揭示了不同水平奥沙利铂诱导神经毒性的特征代谢物。

Metabolomics analysis reveals characteristic metabolites in different levels of oxaliplatin-induced neurotoxicity.

机构信息

Department of Clinical Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, China.

Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, China.

出版信息

J Sep Sci. 2024 Jun;47(11):e2400164. doi: 10.1002/jssc.202400164.

Abstract

Oxaliplatin (L-OHP), a third-generation platinum-based anti-tumor drug, finds widespread application in the first-line treatment of metastatic colorectal cancer. Despite its efficacy, the drug's usage is curtailed by a litany of side effects, with L-OHP-induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high-sensitivity, high-throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra-performance liquid chromatography-high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers.

摘要

奥沙利铂(L-OHP)是第三代铂类抗肿瘤药物,广泛应用于转移性结直肠癌的一线治疗。尽管该药物具有疗效,但由于其诸多副作用,其使用受到限制,其中 L-OHP 诱导的周围神经病变(OIPN)最为严重。这种情况可以分为不同程度的严重程度。采用血清代谢组学,一种高灵敏度、高通量的技术,有望成为一种方法,用于识别生物标志物,用于临床评估和监测不同严重程度的 OIPN 患者。在我们的研究中,我们使用超高效液相色谱-高分辨率质谱分析了不同 OIPN 水平患者的血清代谢物。通过统计学分析和途径富集研究,我们旨在确定潜在的生物标志物和代谢途径。我们的研究结果描述了不同 OIPN 水平患者的血清代谢特征。值得注意的是,途径分析显示与脂质代谢、氨基酸代谢和能量代谢有显著相关性。多变量统计分析和接收器操作特性曲线评估表明,阿那拉胺和甘氨胆酸可能是 OIPN C 和 A 的潜在生物标志物,这表明血清代谢组学可能是一种强大的工具,用于探索患有不同疾病的患者的代谢状态,并发现新的生物标志物。

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