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.