结直肠癌中DLL4的表达与预后及肥胖的关系

Objective： Delta-like ligand 4 (DLL4) is the main ligand of Notch signaling pathway in regulating tumor angiogenesis. Obesity is a major risk factor for colorectal cancer, and its mechanism of promoting tumorigenesis needs further investigation. In the present study, we aimed to investigate the relationship of DLL4 expression with tumor progression and prognosis, as well as obesity in colorectal cancer. Methods： For this study we collected 265 samples of colorectal cancer tissues and paracancerous tissues resected at The First Affiliated Hospital of Xi'an Jiaotong University between January 2012 and December 2013. Immunohistochemistry was used to detect the expression of DLL4. We analyzed the relationship of DLL4 expression with clinicopathological characteristics, prognosis and obesity. The survival data was analyzed by Kaplan-Meier and Cox proportional hazard regression model. Results： The positive expression rate of DLL4 in colorectal cancer tissues was significantly higher than that in adjacent tissues (77.4% vs. 17.7%, P<0.05). The patients with high expression of DLL4 had a lower degree of differentiation, but a greater depth of invasion, a higher lymph node metastasis rate and higher TNM stage (P<0.05). The disease-free survival and overall survival were shorter in DLL4 positive expression group than in the negative group (P<0.001). Cox multiple regression analysis showed that DLL4 expression was an independent prognostic factor for colorectal cancer. The positive expression rate of DLL4 in overweight and obese patients was significantly higher than that in normal weight patients. BMI was positively correlated with the expression level of DLL4 (r_s=0.578, P<0.05). Conclusion： The expression of DLL4 is upregulated in colorectal cancer tissues. Increased expression of DLL4 is associated with poor prognosis of patients, suggesting that DLL4-Notch pathway may be involved in the carcinogenesis and progression of obesity-induced colorectal cancer.