Several studies have predicted the sensitivity of nCRT in colorectal cancer. Imaging modalities that were used for evaluation included CT and ERUS. The frequency of vitamin D insufficiency in patients with locally advanced CRC has not been reported in larger studies. Several studies suggested that the expression levels of four biomarkers (p53, VEGF, p21, and Ki67) were significantly correlated with PCR to nCRT (96.3 %). However, this scoring system showed only 46.3% specificity. Her-2, pre-CEA, and post-CEA were also considered as predictors and of their disadvantages [11, 12]. Altered CEA was proved more significant to reflect the sensitivity of colon cancer to chemotherapy than pre- or post-CEA [13, 14]. So,ΔCEA was utilized as a positive control to compare with 25(OH) D level in our study. There is a hypothesis that alteration of vitamin D receptor may change transcriptional control of 1, 25(OH) 2D3 and impact anti-tumor effect of vitamin D . These results suggest that vitamin D plays a role in inhibiting tumorigenesis of CRC. Our results showed that both serologic levels of pre- and post-nCRT CEA in LARC patients were distinctly higher than the healthy controls (Table 2). We also found that pre-nCRT CEA levels was a risk factor for LARC (OR = 13.145, CI = 1.71-110.31, P = 0 .012, Table 3, respectively).
In our research, the serum concentration of pre-nCRT CEA was much lower than the post-nCRT level ( Table 2), while the concentration of pre-nCRT 25(OH)D was much higher than the post-nCRT level (P < .001, Table 2). It seems that CEA and 25(OH) D had an inverse association with the disease progression. However, there was no significant correlation between these two markers in the serum by Pearson's correlation analysis (Table 4) in our study. Perhaps the small sample volumes reduce the relationship between CEA and 25(OH) D. Due to the limitations of patient management in our hospital; we were unable to measure the serum CEA and 25(OH) D levels at multiple time points in this study.
Many studies found that there is an inverse association between serum 25(OH) D and the risk of CRC [16–18]. We found that both serologic levels of pre- and post- nCRT 25(OH) D in patients with LARC were significantly lower than in healthy individuals. Our research of univariate analysis showed that the serum concentration of pre- and post-nCRT 25(OH) D in male patients and tumor size < 5.0 cm were significantly higher (Table1). A potential explanation could be that a more advanced stage of disease and/or larger tumor size is accompanied with more inflammation, which may lead to lower 25(OH) D3 levels [19, 20]. It could be that the absorption of vitamin D from diet and supplements is impaired due to subclinical mucositis induced by chemotherapy [21, 22]. Andersen et al found that the inverse association between serum 25(OH) D and CRC was more prominent in females than males . A meta-analysis including 1248 cases of CRC suggested that 25(OH) D had stronger inverse associations with colon than with rectal tumors . However, in our study, the serum concentration of pre- and post-nCRT 25(OH) D in rectal and colon tumors were not statistically significant. The serum concentration of pre- and post-nCRT CEA in groups of tumor size༞5.0 cm and lymph node invasion patients not significantly reduced.
A report suggests that low vitamin D levels were found in most cases of breast cancer with advanced tumor stage, large tumors, and positive lymph nodes. In line with our results, the study of Fakih and colleagues observed a threefold higher risk of having vitamin D deficiency in CRC patients. In line with our results, the study of Isenring and colleagues also reported a decrease in 25(OH) D levels in cancer patients receiving chemotherapy . The lower 25(OH)D3 levels and/or the steeper decrease in 25(OH)D3 levels in patients receiving chemotherapy can be induced by changes in lifestyle due to chemotherapy or by chemotherapy directly. The study of Churilla et al., found a higher prevalence of vitamin D deficiency in stage III of disease. But, Some studies show that no difference in the 25(OH) D levels from baseline to six-month follow-up between patients who did and did not receive chemotherapy (P = 0.26), suggesting that chemotherapy may not have the deleterious effects on 25(OH)D levels that we ascribed to increased photosensitivity and potential for gastrointestinal toxicities . And furthermore, Song et al. have found that the associations between vitamin D deficiency and CRC in a large nested case-control study remain valid after adjustment for inflammatory markers .