Wang Lu, Xu Ruize, Wang Mizhu, Wang Menghan, Su Shuai, Nian Yuanyuan, Chen Xin
Tianjin Medical University, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tian Jin, People's Republic of China.
Baotou Medical College, The Second Affiliated Hospital of Baotou Medical College, Baotou, People's Republic of China.
Onco Targets Ther. 2025 Jan 22;18:129-145. doi: 10.2147/OTT.S495066. eCollection 2025.
To explore the relationship and underlying mechanisms between vitamin D and CRC, offering valuable insights into the diagnosis and treatment of CRC.
Serum levels of 1,25(OH)D 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.
Serum levels of 1,25(OH)D 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.
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.
探讨维生素D与结直肠癌(CRC)之间的关系及潜在机制,为CRC的诊断和治疗提供有价值的见解。
采用双抗体夹心测定法测量血清1,25(OH)D水平。生物信息学分析鉴定出维生素D相关的CRC基因,并使用HCT116和HT29细胞系进行验证。通过RT-qPCR分析关键基因表达的变化。
正常组血清1,25(OH)D水平为42.99±6.02µg/mL,结直肠腺瘤(CRA)组为37.06±9.56µg/mL,CRC组为19.00±5.96µg/mL(p<0.05)。各组间维生素D受体(VDR)单核苷酸多态性(SNPs)无显著差异。各组间维生素D相关结肠癌基因存在显著表达差异。套索(LASSO)回归分析确定了5个关键基因。基于这些基因的诊断模型显示出高诊断效率,并且在TCGA-COAD数据集中表现良好。RT-qPCR结果显示,CRC组和CRA组中硬化蛋白结构域蛋白1(SOSTDC1)、蛋白激酶A催化亚基α2(PRKAA2)和癌胚抗原相关细胞黏附分子1(CEACAM1)的表达降低,而基质金属蛋白酶1(MMP1)和细胞周期蛋白D1(CCND1)的表达增加。体外实验表明,骨化三醇抑制HCT116和HT29细胞系的增殖和迁移,并显著改变关键基因的表达。
CRC患者血清维生素D水平显著降低。维生素D已被证明可抑制结肠癌细胞的增殖和迁移,并降低癌基因的表达。因此,维生素D在CRC的诊断和治疗中具有巨大潜力。