Inflammatory-based racial differences in lung cancer biology: diagnostic and prognostic implications

Authors

• CL Meaney
• KA Mitchell
• A Zingone
• DA Brown

Abstract

Population-specific biomarkers of lung cancer diagnosis and prognosis could improve the efficacy of lung cancer screening and treatment options for African Americans (AA) who are disproportionally affected by lung cancer, both in terms of incidence and survival, compared with other ethnic and racial groups in the USA. Given the relationship between inflammation and lung cancer and differences in inflammation between AA and European Americans (EA), we hypothesize that circulating inflammatory markers will be useful biomarkers of diagnosis and prognosis in AA. A broad panel of 30 inflammatory markers was measured in serum from 316 AA cases and 509 AA controls, using the Mesoscale V-Plex assay. This allowed a direct comparison of inflammatory profiles of AA to a parallel study in EA, to establish the need for population-specific diagnostic markers to improve the cancer screening process and improve overall lung cancer outcomes. Integration of comprehensive clinical, genetic ancestry (ancestry informative markers), demographic, and genetic information (GWAS) allowed us to explore the factors driving modulation of inflammatory marker expression in this AA cohort. Distinct differences in inflammatory profiles, particularly macrophage-derived proteins, were observed between EA and AA populations. Levels of MDC, MIP-1a, MIP-1b and IL-16 were significantly higher in AA healthy controls compared with EA, while levels of Eotaxin were lower in AA. These data suggest a higher basal level of macrophage-derived inflammation in AA. We also discovered a significant relationship between macrophage-derived inflammation proteins with lung cancer risk, that we did not observe in EA. The findings suggest that a macrophage-derived inflammatory signature is diagnostic for lung cancer in AA that is not evident in EA, raising the possibility that risk prediction and classification models may need to account for racial differences in biomarker profiles. Moreover, it suggests that different pathways are involved in lung cancer etiology in AA and EA. Finally, given that macrophages and macrophage-derived proteins can mediate resistance to immunotherapy, our results also raise the possibility of racial differences in immunotherapy efficacy.

Scientific Focus Area: Health Disparities

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