Prognostic value of circulating vitamin D binding protein, total, free and bioavailable 25-hydroxy vitamin D in patients with colorectal cancer

Abstract

Numerous studies have suggested that there was a significantly positive association between circulating total 25-hydroxyvitamin D (25(OH)D) and survival in colorectal cancer patients. Moreover, plasma vitamin D was also found significantly associated with the concentration of vitamin D binding protein (VDBP). However, there was no paper to clarify the prognostic value of VDBP, free and bioavailable 25(OH)D in colorectal carcinogenesis. The aim of this study was to comprehensively assess the prognostic value of VDBP, total, free and bioavailable 25(OH)D in stage I-III colorectal cancer patients. A total of 206 colorectal cancer patients were enrolled in this prospective study. Preoperative plasma total 25(OH)D and VDBP concentrations were measured by direct enzyme-linked immunosorbent assay, and albumin concentration was measured by Beckman automatic biochemical analyzer. Free and bioavailable 25(OH)D concentrations were calculated based on the concentrations of plasma VDBP, total 25(OH) D and albumin. X-title program was used to determine the optimal cut-off values of VDBP, total, free and bioavailable 25(OH)D. Results showed that elevated free and bioavailable 25(OH)D were significantly associated with better 5-year overall survival (OS) by univariate analysis. By multivariate cox analysis, we also found that the high level of free 25(OH)D (HR = 0.442, 95%CI = 0.238-0.819, P < 0.010) could be identified as an independent factor for better OS. In conclusion, our study suggested that higher levels of free and bioavailable 25(OH)D were associated with better OS in stage I-III colorectal cancer patients. Moreover, free 25(OH)D could be considered as an independent prognostic biomarker for OS.

Keywords: 25(OH)D; VDBP; colorectal cancer; overall survival; prognosis.

Figure 1. X-tile analyses for 5-year overall survival

The sample of CRC patients was equally divided into training and validation sets. X-tile plots of training sets were shown in the left panels, with plots of matched validation sets shown in the smaller inset. The optimal cut-off values highlighted by the black circles in left rectangular panels were also shown in histograms of the entire cohort (middle panels), and Kaplan–Meier plots were displayed in right panels. p values were determined by using the cut-off values defined in training sets and applying them to validation sets. The optimal cut-off values of Free 25(OH)D and Bioavailable 25(OH)D for OS were 0.01–0.01 pg/ml, and 0.58–1.03 ng/ml, respectively. (A) Free 25(OH)D. (B) Bioavailable 25(OH)D. CRC, colorectal cancer; VDBP, vitamin D binding protein; OS, overall survival.