Plasma proteomic profiles reveal immune modulation by immunonutrition in GI cancer.

BACKGROUND: Gastrointestinal (GI) cancer patients undergoing surgery often face immunosuppression, increasing postoperative risk. Immunomodulatory enteral nutrition (IEN) may enhance immune function and recovery, but mechanisms remain unclear. This study compared plasma proteomic profiles of patients receiving IEN versus standard enteral nutrition (SEN) to explore pathways linked to outcomes. METHODS: This analysis extended a previously published randomized clinical trial in GI cancer patients who received SEN or IEN postoperatively, with 50 patients in each group. The IEN was rich in arginine, nucleotides, vitamin B12, chloride, vitamin C, selenium, chromium, and molybdenum. Plasma samples were analyzed using mass spectrometry-based proteomics (MassLynx v4.1 and Progenesis v4.1). Proteins consistently detected across replicates (database search P < 0.05) were identified. Clinical outcomes, including complications and biochemical markers, were integrated with proteomic findings to interpret biological mechanisms. RESULTS: Distinct proteomic profiles were observed. The IEN group showed higher levels of complement proteins (C3, C5, C9), inter-alpha-trypsin inhibitor heavy chain H2, pregnancy zone protein, immunoglobulins, and apolipoproteins-proteins linked to immune modulation, tissue repair, and inflammation control. The SEN group displayed elevated acute-phase proteins and coagulation factors, including fibrinogen and serum amyloid A-4, consistent with a pro-inflammatory, hypercoagulable state. These differences paralleled clinical results, with the IEN group experiencing fewer complications and improved albumin/globulin ratios. CONCLUSIONS: This exploratory study suggests that immunonutrition may modulate complement activation and immune pathways, supporting better postoperative outcomes in GI cancer patients. The proteomic profile provides evidence that supports a mechanistic hypothesis underlying the observed clinical benefits. Future quantitative proteomics with larger cohorts is warranted to validate these findings and optimize perioperative nutrition strategies.