Prognostic and monitoring relevance of systemic nitric oxide in patients with colon cancer.

Reliable and minimally invasive biomarkers are needed for early detection, prognosis, and monitoring of colon cancer (CC). The aim of our study was to evaluate the role of systemic nitric oxide (NO) in inflammation and tumor progression and its diagnostic and prognostic value in CC. This prospective monocentric case-control study included 130 patients with non-metastatic CC and 100 healthy subjects. Clinical and pathological data were collected, and blood cell count-derived ratios were calculated. Systemic nitrite and cytokines levels were assessed using Griess method and ELISA respectively. Tumor-infiltrating immune cells were evaluated by immunohistochemistry in 44 patients. ROC curves, Kaplan-Meier, and log-rank tests were performed to highlight the diagnostic and prognostic value of NO production in patients followed for two years. Systemic plasma nitrite levels were significantly higher in patients than in controls (p < 0.0001), and correlated significantly and positively with most inflammatory and tumor markers and CD68 cells and CD4 T cells, but negatively with IL-6, albumin and CD8 T cells. Interestingly, high nitrite levels were associated with tumor progression (cancer stage, tumor size, lymph node ratio). ROC analysis confirmed a high diagnostic performance (AUC = 0.88 for patients vs. controls; AUC = 0.71 for early vs. advanced stages). Prognostically, elevated nitrite levels predicted postoperative complications (AUC = 0.67; p log-rank<0.0001), reduced recurrence-free survival (AUC = 0.70; p log-rank = 0.03), and reduced overall survival (AUC = 0.75; p log-rank = 0.04). Our findings indicate that systemic nitrite levels are closely linked to inflammation and tumor progression in CC and demonstrate strong predictive accuracy, emerging as a promising biomarker for patient management.