BACKGROUND

Cancer-associated anorexia (AN) and cachexia are frequent and debilitating complications of cancer, driven by systemic inflammation and metabolic dysregulation. Lipocalin 2 (LCN2) has been implicated in immune-metabolic integration and central appetite control, however data in cancer patients are limited.

This study aimed to assess circulating LCN2 in patients with gastrointestinal cancers (GI-CP) and to evaluate its association with AN, levels of systemic inflammatory cytokines (IL-6, -8, -10, -15, -18, and TNF-α), body weight change, and level of muscularity.

METHODS

Twenty-eight GI-CP naïve to treatment and 10 controls were enrolled. AN was diagnosed in 50% of GI-CP by the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score ( 30).

Serum LCN2 concentrations were measured by ELISA, and cytokines were quantified using xMAP assay. Clinical, nutritional, and body composition parameters assessed by CT-scan were collected, and association(s) between LCN2 and inflammatory markers were analyzed.

RESULTS

In GI-CP, predominantly represented by colorectal cancer, LCN2, IL-6, IL-8, IL-15, and TNF-α were higher than controls (p < 0.05).

In GI-CP, LCN2 showed positive correlations with IL-6 (rho = 0.862; p < 0.001) and IL-8 (rho = 0.789; p < 0.001). LCN2 levels were higher in GI-CP with AN vs.

control (p = 0.003), but not between anorexic vs. non-anorexic GI-CP, and in GI-CP with body weight loss compared to those with weight-stable (p = 0.031) and vs.

controls (p < 0.001). LCN2 was higher in GI-CP with AN and body weight loss compared to those without AN and body weight stable (p = 0.046) and in GI-CP with low muscle mass and body weight loss compared with those with body weight stable and high muscularity (p = 0.028).

CONCLUSION

Overall, these findings suggest that LCN2 may reflect the combined burden of inflammation and cachexia-related features in GI cancer.