Plasma signals of lung tumor promotion for molecular cancer prevention.

Summary

This multi-cohort study developed and validated a 14-protein plasma signature that predicts lung cancer more than 5 years before diagnosis, with elevation in smokers and particulate matter–exposed individuals. The biology links to lung myeloid and alveolar cells and suggests enrichment strategies for preventive interventions such as IL‑1β blockade.

Key Findings

• A 14-protein plasma signature predicted lung cancer >5 years before diagnosis and was validated across eight cohorts.
• Signature levels were higher in current smokers and individuals exposed to particulate matter.
• Biological links to lung myeloid and alveolar cells were identified; epithelial lineages in EGFR-driven adenocarcinoma converged on a keratin8 intermediate state.

Clinical Implications

Could enable targeted enrollment into preventive trials (e.g., IL-1β inhibition) and risk-adapted screening pathways, reducing number needed to treat by focusing on biologically high-risk individuals.

Limitations

• Observational design without interventional validation of risk-guided prevention.
• Cohort heterogeneity and potential residual confounding may influence performance estimates.

Future Directions

Prospective implementation trials testing biomarker-guided prevention (e.g., IL‑1β blockade) and integration with imaging/radiomics to refine individualized risk.