Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy

Nat Commun. 2020 Oct 2;11(1):4946. doi: 10.1038/s41467-020-18742-9.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Cohort Studies
  • Factor Analysis, Statistical
  • Genomics*
  • Humans
  • Immunotherapy / adverse effects*
  • Microfilament Proteins / metabolism
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor
  • LCP1 protein, human
  • Microfilament Proteins