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Peer-reviewedCC BYFrontiers in nutrition

Circulating lipocalin-2 is associated with systemic inflammation and cachexia-related features in patients with gastrointestinal cancer

  • Federica Tambaro1
  • Giovanni Imbimbo1
  • Dario Coletti2
  • Roberta De Tullio3
  • Elena Belloni4
  • Giuseppe Nigri4
  • Paola Costelli5
  • Maurizio Muscaritoli1
  • Alessio Molfino1
5 affiliations
  1. 1Department of Translational and Precision Medicine, Sapienza University of Rome , ,
  2. 2DAHFMO Unit of Histology and Medical Embryology, and Interuniversity Institute of Myology, Sapienza University of Rome , ,
  3. 3Department of Experimental Medicine (DIMES), Section of Biochemistry, University of Genova , ,
  4. 4Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome , ,
  5. 5Department of Clinical and Biological Sciences, University of Turin , ,
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{tambaro2026circulating,
  title = {{Circulating lipocalin-2 is associated with systemic inflammation and cachexia-related features in patients with gastrointestinal cancer}},
  author = {Federica Tambaro and Giovanni Imbimbo and Dario Coletti and Roberta De Tullio and Elena Belloni and Giuseppe Nigri and Paola Costelli and Maurizio Muscaritoli and Alessio Molfino},
  journal = {Frontiers in nutrition},
  year = {2026},
  month = oct,
  doi = {10.3389/fnut.2026.1937525},
  url = {https://europepmc.org/article/PMC/PMC13724323},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Circulating lipocalin-2 is associated with systemic inflammation and cachexia-related features in patients with gastrointestinal cancer
AU  - Federica Tambaro
AU  - Giovanni Imbimbo
AU  - Dario Coletti
AU  - Roberta De Tullio
AU  - Elena Belloni
AU  - Giuseppe Nigri
AU  - Paola Costelli
AU  - Maurizio Muscaritoli
AU  - Alessio Molfino
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in nutrition
DO  - 10.3389/fnut.2026.1937525
UR  - https://europepmc.org/article/PMC/PMC13724323
AB  - 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.
SN  - 2296-861X
ER  -