PP295 - CIRCULATING NEUROTROPHIC FACTORS AS MARKERS OF NEUROMUSCULAR JUNCTION INTEGRITY IN PATIENTS WITH GASTROINTESTINAL CANCER

PP295

CIRCULATING NEUROTROPHIC FACTORS AS MARKERS OF NEUROMUSCULAR JUNCTION INTEGRITY IN PATIENTS WITH GASTROINTESTINAL CANCER

F. Tambaro^1,*, G. Imbimbo¹, S. Orlando¹, C. Gallicchio¹, M. I. Amabile², P. Costelli³, M. Muscaritoli¹, A. Molfino^1,4

¹Department of Translational and Precision Medicine, ²Department of Surgical Sciences, Sapienza University, Rome, ³Department of Clinical and Biological Sciences, University of Turin, Turin, ⁴Department of Interdisciplinary Studies on WellBeing, Health and Environmental Sustainability (BeSSA), Sapienza University, Rome, Italy

Rationale: Cancer cachexia (CC) is characterized by muscle wasting and may involve early alterations of the nerve-muscle axis, including dysfunction of neuromuscular junction (NMJ). We investigated whether circulating neurotrophic factors related to NMJ integrity differ in patients with gastrointestinal (GI) cancer vs controls and are associated with CC and/or low muscularity.

Methods: 31 patients with GI cancer and 9 healthy controls were studied. CC was defined according to Fearon criteria. Circulating brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurotrophin-4 (NT-4) were measured by xMAP assay. Associations with cancer, CC, and muscularity were evaluated. Muscularity was assessed by sex-specific internal L3 skeletal muscle index cut-offs, defining high muscularity mass (HMM) and low muscularity mass (LMM).

Results: Compared with controls, patients with GI cancer showed lower circulating BDNF, GDNF, and NT-4 levels (p<0.05). Both HMM and LMM groups had lower BDNF than controls (p=0.013 and p=0.001). NT-4 was lower in both HMM and LMM than controls (p=0.039 and p<0.001), with a significant lower level in LMM vs HMM (p=0.001). GDNF was lower in HMM vs controls (p=0.020). According to CC, BDNF was lower in both patients with/without CC vs controls (p=0.006 and p=0.004), and NT-4 was similarly reduced in both groups vs controls (both p<0.001). GDNF was lower in patients with CC vs controls (p=0.029).

Conclusion: Circulating neurotrophic factors linked to NMJ biology were reduced in GI cancer, suggesting the presence of early nerve-muscle alterations. BDNF and NT-4 appear to discriminate patients with cancer from controls regardless of CC, whereas GDNF may be more closely related to overt CC. These factors should be further investigated as circulating biomarkers of NMJ impairment in cancer-associated muscle wasting.

Disclosure of Interest: None declared