Anemia-Driven Phenotypes in Lung Cancer: Linking Inflammation and Sarcopenia

Background/Objectives: Lung cancer remains a leading cause of cancer-related mortality and is characterized by complex tumor-host interactions, including systemic inflammation, metabolic dysregulation, and immune imbalance. This study aimed to evaluate whether a diagnosis of anemia reflects underlying inflammatory burden and to explore phenotype-based interactions between anemia, inflammation, and muscle depletion in lung cancer patients. Methods: A retrospective cohort study was conducted, including 70 patients diagnosed with lung cancer between 2019 and 2023. Anemia was defined using standard hemoglobin thresholds (<12 g/dL in women, <13 g/dL in men). Systemic inflammation was assessed using complete blood count-derived indices (NLR, PLR, SII, SIRI, and AISI), both individually and combined into a cumulative inflammatory score. Sarcopenia was evaluated through CT-based quantification of skeletal muscle area at the L3 level. Patients were stratified into four phenotypes based on anemia status, inflammatory burden, and sarcopenia. Statistical analyses like Mann-Whitney U, Kruskal-Wallis with Dunn post hoc testing, and univariate logistic regression were used. Results: Anemia was present in 44.3% of patients and was associated with a significantly higher inflammatory score compared to non-anemic patients (median 5 [IQR 4-5] vs. 4 [3-5], p = 0.024). Among inflammatory markers, PLR was significantly associated with anemia (OR = 4.94, 95% CI: 1.57-15.52, p = 0.004). The cumulative inflammatory score showed a non-significant association with anemia (OR = 1.28, 95% CI: 0.93-1.75, p = 0.124). Phenotype-based analysis revealed significant differences in skeletal muscle area (p = 0.004), with the sarcopenic-inflammatory phenotype exhibiting significantly lower muscle mass compared to other groups. No associations were observed between phenotypes and tumor stage or histological subtype. Conclusions: Anemia in lung cancer patients is closely associated with systemic inflammation and may reflect underlying biological vulnerability rather than tumor-specific characteristics. A phenotype-based approach integrating anemia, inflammatory markers, and sarcopenia provides a more comprehensive understanding of disease heterogeneity and may improve risk stratification. Further studies are needed to validate these findings and assess their prognostic implications.