Dysregulated iron metabolism in lung cancer: integrating serum biomarkers, histopathological features, and molecular phenotypes

Lung cancer remains the leading cause of cancer-related mortality worldwide despite substantial advances in molecular diagnostics, targeted therapies, and immunotherapy. Increasing evidence indicates that dysregulated iron metabolism is a critical driver of tumor initiation, progression, metastasis, oxidative stress, ferroptosis, and therapeutic resistance. Alterations in circulating iron biomarkers, including ferritin, transferrin, transferrin saturation, and total iron-binding capacity, have emerged as promising indicators of systemic iron homeostasis and tumor aggressiveness. This narrative review summarizes current evidence on the relationship between iron metabolism and lung cancer, emphasizing its association with histopathological grading, molecular immunophenotypes, oxidative stress, and ferroptosis. Relevant literature was critically evaluated to examine iron regulatory pathways, serum iron biomarkers, and emerging therapeutic strategies. Current findings demonstrate that increased ferritin expression, enhanced transferrin receptor-mediated iron uptake, reduced ferroportin activity, and disrupted iron homeostasis contribute to molecular heterogeneity, inflammatory remodeling of the tumor microenvironment, and unfavorable clinical outcomes. Furthermore, ferroptosis has emerged as a promising therapeutic target linking iron metabolism with precision oncology. Although circulating iron biomarkers show potential as complementary prognostic indicators, their routine clinical application is limited by methodological heterogeneity and insufficient prospective validation. Future multicenter studies integrating iron biomarkers with molecular profiling are essential to establish their clinical utility in personalized lung cancer management.