Circulating Metabolic Markers Identify Patients at Risk for Tumor Recurrence: A Prospective Cohort Study in Colorectal Cancer Surgery.

Objective: To investigate the spermidine pathway capability to predict patients at risk for tumor recurrence following colorectal cancer (CRC) surgery.

Background: Recurrence rates after CRC surgery remain at about 20% despite an optimal technique and adjuvant therapy when necessary. Identification of risk biomarkers of recurrence is an unmet need. The spermidine pathway is indispensable for cell proliferation and differentiation, and is suggested to accelerate tumor spread.

Methods: This was a prospective cohort study of patients undergoing CRC surgery from 2015 to 2018. Plasma samples were collected before surgery and on postoperative day 4, and the spermidine pathway was assessed through mass spectrometry. Oncological outcomes were registered.

Results: A total of 146 patients were included and 24 (16.4%) developed tumor recurrence. Higher levels of preoperative spermidine pathway components (spermidine, spermine, spermidine synthase enzyme, and spermine/arginine balance) were positively associated with recurrence. Surgery promoted a decrease in these pathway elements. The greater the decline was, the lower the risk of recurrence. Preoperative spermidine over the cut-off of 0.198 µM displayed a 4.69-fold higher risk of recurrence. The spermine synthase enzyme behaved in the opposite direction.

Conclusions: The spermidine pathway is associated with tumor recurrence following CRC surgery and, after confirmation in larger cohorts, could be translated as a risk biomarker of recurrence into clinical practice.