IARC 60th Anniversary - 19-21 May 2026
Session : 19/05/26 - Posters
Integrating Proteins and Metabolites to Reveal Biological Connections Underlying Air Pollution-Associated Lung Cancer
TANG Z. 2, WANG Y. 1, SARNAT J. 2, DIVER W. 1, EVERSON T. 2, DEUBLER E. 1, HOFFMAN S. 2, TAN Y. 2, KESARWALA A. 4, TURNER M. 3,6, JOHANSSON M. 5, ROBBINS H. 5, MARSIT C. 2, PATEL A. 1, LIANG D. 2
1 American cancer society, Atlanta, United States; 2 Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, United States; 3 Universitat Pompeu Fabra, Barcelona, Spain; 4 Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, United States; 5 Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France; 6 Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain
Background: Single-omics studies suggest that proteins and metabolites involved in inflammation, immune modulation, and cell dysregulation may link air pollution to lung cancer. However, these approaches provide only a partial view of complex biological processes.
Objective: We integrated proteomics and metabolomics to characterize a multi-omics network connecting air pollution and lung cancer, aiming for a more comprehensive understanding of the underlying biology.
Methods: We analyzed pre-diagnosis plasma proteomics and metabolomics profiles from 106 lung cancer cases and 13 controls in the CPS-II Nutrition Cohort (1998-2001). A total of 165 air pollution-associated proteins and 486 metabolites, identified in two previous independent investigations within the same cohort, were integrated using Data Integration Analysis for Biomarker discovery using Latent Components within the ‘mixOmics’ R package. Proteins and metabolites selected in the latent components were subsequently used for both separate and joint pathway enrichment analyses.
Results: Using a posterior multi-omics integration workflow, we identified three latent components comprising 20, 20, and 50 proteins and 6, 18, and 30 metabolites, respectively. These components, showing moderate to strong intercorrelations, were associated with air pollution exposures and partially discriminated lung cancer cases from controls. Joint pathway analysis identified six pathways at a false discovery rate < 0.05. Four signaling pathways - cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and sphingolipid signaling - were also consistently detected in single-omics pathway analyses (P <0.1), providing mutual validation. These pathways were associated with chemokines (e.g. CX3CL1, CXCL9), interleukins (e.g. IL32, IL-1B), tumor necrosis factor receptor superfamily (e.g. TNF-R1), sphingolipids (e.g. behennoyl dihydrosphingomyelin), and glycosphingolipids.
Conclusion: The selected molecules and their enriched pathways converged on key processes related to inflammatory signaling, cell survival, immune responses, and metabolic regulation. These findings provide novel insights into biological links between air pollution and lung cancer and reinforce, while extending, evidence from prior single-omics analyses.