Lu Wang,1,2,* Ruize Xu,2,* Mizhu Wang,2 Menghan Wang,2 Shuai Su,1 Yuanyuan Nian,2 Xin Chen1 

1Tianjin Medical University, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tian Jin, People’s Republic of China; 2Baotou Medical College, The Second Affiliated Hospital of Baotou Medical College, Baotou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xin Chen, Tianjin Medical University, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tian Jin, People’s Republic of China, Email xchen03@tmu.edu.cn Yuanyuan Nian, Baotou Medical College, the Second Affiliated Hospital of Baotou Medical College, Baotou, People’s Republic of China, Email nianyuanyuannina@163.com

Objective: To explore the relationship and underlying mechanisms between vitamin D and CRC, offering valuable insights into the diagnosis and treatment of CRC.
Materials and Methods: Serum levels of 1,25(OH)2D3 were measured using a double-antibody sandwich assay. Bioinformatics analysis identified vitamin D-related CRC genes, which were validated using HCT116 and HT29 cell lines. Changes in hub gene expression were analyzed via RT-qPCR.
Results: Serum levels of 1,25(OH)2D3 were 42.99± 6.02μg/mL in the normal group, 37.06± 9.56μg/mL in the CRA group, and 19.00± 5.96μg/mL in the CRC group (p< 0.05). No significant differences were observed in VDR SNPs among the groups. Significant expression differences were detected in vitamin D-related colon cancer genes across the groups. LASSO regression analysis identified 5 key genes. The diagnostic model based on these genes demonstrated high diagnostic efficiency and performed well in the TCGA-COAD dataset. RT-qPCR results showed that SOSTDC1, PRKAA2, and CEACAM1 expressions decreased in the CRC and CRA groups, while MMP1 and CCND1 expressions increased. In vitro experiments indicated that calcitriol inhibits the proliferation and migration of HCT116 and HT29 cell lines and significantly alters the expression of hub genes.
Conclusion: Serum vitamin D levels are significantly lower in CRC patients. Vitamin D has been shown to inhibit the proliferation and migration of colon cancer cells and reduce the expression of oncogenes. Therefore, vitamin D holds substantial potential for the diagnosis and treatment of CRC.

Keywords: colorectal cancer, colorectal adenoma, vitamin D, vitamin D receptor, bioinformatics