Serum YKL-40, but Not Relaxin-2, Shows Diagnostic Utility as an Adjunct Biomarker in Colorectal Cancer

Despite the availability of conventional serum markers for colorectal cancer (CEA, CA 19-9), there remains a need for more sensitive and specific biomarkers, particularly for early-stage detection. This study evaluated the diagnostic usefulness of serum Relaxin-2 (RLN2) and Chitinase-3-like protein 1 (YKL-40) as potential adjunct markers in patients with CRC. Serum concentrations of all the proteins were measured using a multiplexing assay and CMIA and were subsequently compared using non-parametric statistical tests. The concentrations of YKL-40, CEA, and CA 19-9 were elevated in CRC patients relative to controls (p < 0.05), but not so for RLN2. The concentrations of YKL-40 were also significantly elevated in patients undergoing chemotherapy or preoperative radiotherapy referral. Kruskal-Wallis and post-hoc testing found that YKL-40 and CEA were associated with tumor progression, but RLN2 and CA 19-9 were increased primarily in advanced, metastatic disease. No statistically significant differences in marker levels were observed between cancer subtypes or between histologic grades. Performance analysis for diagnostic purposes showed YKL-40 was moderately sensitive (65%) but very specific (77.5%), and its AUC was 0.702, higher than CA 19-9 (AUC = 0.632) but lower than CEA (AUC = 0.869) (all p < 0.05). RLN2 did not reach statistical significance (AUC = 0.593, p = 0.09). Correlation analysis demonstrated the best correlation with disease stage for CEA and weaker positive correlations for YKL-40, CA 19-9, and RLN2. These findings suggest that YKL-40 may serve as a useful adjunct serum biomarker for CRC diagnosis, especially when combined with conventional markers such as CEA.