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Abstract
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.
Immunotherapy, the reactivation of the immune system to recognize cancer cells, can be accompanied by severe adverse effects. Here, the authors use pharmacovigilance and genomic data to be able to predict which patients might be susceptible to such severe events.
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1 The University of Texas Health Science Center at Houston McGovern Medical School, Department of Biochemistry and Molecular Biology, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401)
2 Shanghai Jiao Tong University, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)
3 Capital Medical University; Peking University Ninth School of Clinical Medicine, Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Beijing, China (GRID:grid.24696.3f) (ISNI:0000 0004 0369 153X)
4 The University of Texas MD Anderson Cancer Center, Department of Bioinformatics and Computational Biology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776)
5 The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Division of Radiation Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776)
6 Oregon Health and Science University, Department of Cell, Development, and Cancer Biology, Knight Cancer Institute, Portland, USA (GRID:grid.5288.7) (ISNI:0000 0000 9758 5690)
7 Shanghai Jiao Tong University, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); Shanghai Jiao Tong University, Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)
8 The University of Texas Health Science Center at Houston McGovern Medical School, Department of Biochemistry and Molecular Biology, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401); The University of Texas Health Science Center at Houston, Center for Precision Health, Houston, USA (GRID:grid.267308.8) (ISNI:0000 0000 9206 2401)