摘要
目的探讨Delta-like ligand 4(DLL4)的表达与结直肠癌进展、预后及肥胖的关系。方法选取西安交通大学第一附属医院于2012年1月至2013年12月行手术切除的结直肠癌组织265例,应用免疫组织化学法检测肿瘤组织及其癌旁组织中的DLL4表达情况,分析DLL4表达与肿瘤临床病理特征、预后及肥胖的关系,采用Kaplan-Meier法及Cox比例风险回归模型分析生存数据。结果结直肠癌组织中DLL4的阳性表达率明显高于癌旁组织(77.4%vs.17.7%,P<0.05),DLL4高表达的患者肿瘤分化程度低,且浸润深度、淋巴结转移率、TNM分期均升高(P<0.05)。DLL4阳性表达组无病生存期和总体生存期均较阴性组缩短(P<0.001)。Cox多元回归分析显示,DLL4表达上调是结直肠癌预后不良的独立危险因素。超重和肥胖患者的DLL4阳性表达率明显高于正常体重的患者,体质指数与DLL4表达水平呈正相关(r s=0.578,P<0.05)。结论DLL4在结直肠癌组织中表达上调,DLL4的高表达与患者预后不良密切相关,提示DLL4-Notch信号通路参与结直肠癌进展,并且与肥胖促进结直肠癌发生发展相关。
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.
作者
李潇
罗玉梅
张娜
和水祥
朱琨
党诚学
初大可
LI Xiao;LUO Yumei;ZHANG Na;HE Shuixiang;ZHU Kun;DANG Chengxue;CHU Dake(The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061;Second Outpatient Department of Chengdu Military Region,Chengdu 610015,China)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2020年第2期225-229,共5页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金面上项目(No.81201927,81672460)
陕西省重点研发计划项目(No.2017SF-110,2017KJXX-07,2019SF-012)~~
