Diagnostic and prognostic significance of circulating secreted frizzled‐related protein 5 in colorectal cancer

Abstract

BackgroundSecreted 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)MethodsPlasma cSFRP5 concentrations were measured using enzyme‐linked immunosorbent assay (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).ResultsPatients 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, adjusted for patient age, sex, plasma age and collection institution, peaked in stage II versus I (p < 0.0001), III (p = 0.0002) and IV (p < 0.0001), were lowest in stage I versus III (p = 0.0002) and IV (p = 0.0413), with no difference between stage III and IV. Elevated cSFRP5 levels predicted longer overall survival in stages 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).ConclusionThis study confirms cSFRP5 levels are elevated in CRC compared to healthy control and reveals a correlation between elevated cSFRP5 and overall survival in stages II‐III disease.