High serum YKL-40, but not plasma VEGF and serum HER2, as a prognostic biomarker of short survival in patients with metastatic colorectal cancer

Abstract

14517 Purpose: To evaluate the prognostic value of plasma VEGF, serum YKL-40 and HER2 before, during and after chemotherapy in patients with their first manifestation of metastatic colorectal cancer (mCRC). Patients and Methods: Prospective, longitudinal study of 105 patients (60 men and 45 women, median age 65, range 36–79 years, PS 0–2) from 7 centers referred with their first manifestation of mCRC. The patients were treated with Oxaliplatin 130 mg/m2 day 1 and Capecitabine 2000 mg/m2 days 1–14 every 3 weeks. Median follow-up was 1.8 years. 92 patients had progression and 62 died. The biomarkers were determined by ELISAs. Results: Pretreatment plasma VEGF (median 90 ng/l, range 3–2622, 37% had high level >137 ng/l) and serum YKL-40 (102 μg/l, 28–692, 40% had higher level than the age-corrected 95th percentile in healthy individuals) were significantly (p<0.001) elevated in the patients compared to normal levels. Serum HER2 was not elevated (7.90 μg/l, 3.6–92, 6% had high level >15 μg/l). Pretreatment serum YKL-40 was higher in patients who died compared to those alive (115 vs. 75 μg/l, p=0.004). No differences in plasma VEGF (97 vs. 85 ng/l, p=0.27) and serum HER2 (8.0 vs. 7.4 μg/l, p=0.16) were found. Univariate Cox analysis showed that plasma VEGF and serum HER2 before treatment or during follow-up could not predict progression-free and overall survival. Pretreatment serum YKL-40 (log transformed, scored as a continuous variable) was in a univariate analysis a prognostic biomarker of overall survival (HR=1.8, 95% CI: 1.3–2.6, p=0.0006), but not of progression- free survival (p=0.81). Multivariate Cox analysis (age, sex, number of organs with metastasis, pretreatment serum YKL-40 (continuous variable)) showed that serum YKL-40 (HR=1.8, 95% CI: 1.3–2.6, p=0.001) and possible the number of organs with metastasis (p=0.06) were independent predictors of overall survival. During follow-up, a high serum YKL-40 (log transformed continuous variable and landmark time) predicted shorter time to progression (HR=1.5, 95% CI 1.1–2.1, p=0.01) and overall survival (HR=1.7, 95% CI 1.2–2.4, p=0.005). Conclusion: Serum YKL-40 is a prognostic biomarker of overall survival and during follow-up also of progression-free survival in patients with mCRC. No significant financial relationships to disclose.