Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, 77030, USA.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200217, Shanghai, China.
Nat Commun. 2020 Oct 2;11(1):4946. doi: 10.1038/s41467-020-18742-9.
Immune-related adverse events (irAEs), caused by anti-PD-1/PD-L1 antibodies, can lead to fulminant and even fatal consequences and thus require early detection and aggressive management. However, a comprehensive approach to identify biomarkers of irAE is lacking. Here, we utilize a strategy that combines pharmacovigilance data and omics data, and evaluate associations between multi-omics factors and irAE reporting odds ratio across different cancer types. We identify a bivariate regression model of LCP1 and ADPGK that can accurately predict irAE. We further validate LCP1 and ADPGK as biomarkers in an independent patient-level cohort. Our approach provides a method for identifying potential biomarkers of irAE in cancer immunotherapy using both pharmacovigilance data and multi-omics data.
免疫相关不良反应(irAEs)是由抗 PD-1/PD-L1 抗体引起的,可导致暴发性甚至致命的后果,因此需要早期检测和积极管理。然而,目前缺乏一种全面的方法来识别 irAE 的生物标志物。在这里,我们利用一种结合了药物警戒数据和组学数据的策略,评估了多组学因素与不同癌症类型 irAE 报告比值比之间的关联。我们确定了 LCP1 和 ADPGK 的双变量回归模型,可以准确预测 irAE。我们进一步在独立的患者水平队列中验证了 LCP1 和 ADPGK 作为生物标志物的作用。我们的方法提供了一种使用药物警戒数据和多组学数据识别癌症免疫治疗中潜在 irAE 生物标志物的方法。