Circulating SFRP5 levels are elevated in colorectal cancer and correlate with overall survival in stage II-III disease

Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC). Plasma cSFRP5 concentrations were measured using ELISA in healthy donors (n=133), individuals diagnosed with CRC (n=449), colorectal polyps (n=85), and medical conditions in other organs including cancer, inflammation, and benign states (n=64). Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p<0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps, and CRC were 0.814 (p<0.0001), 0.763 (p<0.0001), and 0.762 (p<0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p<0.0001), tumour stage (p<0.0001), and histological differentiation (p=0.0273). Levels peaked in stage II versus I (p<0.0001), III (p=0.0007), or IV (p<0.0001), and were higher in stage III versus I (p=0.0007) and IV (p=0.0054), with no difference between I and IV. Elevated cSFRP5 levels predicted longer overall survival in stage II-III CRC (univariate: HR 1.82, 95% CI 1.02-3.26, p=0.024; multivariable: HR 2.34, 95% CI 1.12-4.88, p=0.015). This study confirms elevated cSFRP5 levels in CRC and reveals a correlation between elevated cSFRP5 and overall survival in stage II-III disease.