D2.445 - Systemic Nitric Oxide: a promising inflammatory biomarker for early detection, prognosis, and monitoring of patients with colon cancer

Reliable and minimally invasive biomarkers are needed for early detection, prognosis, and monitoring 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 diagnosis and prognosis value in CC.

This prospective monocentric case-control study included 130 patients with non-metastatic CC and 100 healthy controls. Clinical and pathological data were collected, and systemic NO levels were measured using the Griess method. Inflammatory markers, blood cell count–derived ratios, and cytokines were also assessed. Tumor-infiltrating immune cells were also evaluated by immunohistochemistry in 44 patients. ROC curves, Kaplan–Meier, and log-rank tests were applied to highlight the diagnosis and prognosis value of NO in patients followed for two years.

Systemic NO 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 NO levels were associated with tumor progression (cancer stage, tumor size, lymph node ratio). ROC analysis confirmed a strong diagnosis performance (AUC=0.88 for patients vs. controls; AUC=0.71 for early vs. advanced stages). Prognostically, elevated NO 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 NO is closely linked to inflammation and tumor progression in CC. NO also exhibits high diagnosis and prognosis accuracy, emerging as a promising biomarker for patient management.