·论著·

胃癌中Notch1、DLL4和HES1的表达及其与临床病理特征和预后的关系

何黎黎张富花张锦华庄剑波张建刚韩俭

摘要：目的通过检测Notch信号系统中的Notch1、DLL4和HES1蛋白在胃癌组织中的表达，分析它们与患者临床病理特征及生存期之间的关系，探索胃癌发生发展的机制。方法 将胃癌、癌旁组织制作组织芯片，采用免疫组化法检测Notch1、DLL4和HES1的表达，随访患者，分析它们的表达与患者临床病理特征及生存期之间的关系。结果Notch1在胃癌、癌旁及对照组中的表达阳性率分别为48.30%、25.00%和16.67%，三者间差异有统计学意义(P<0.05)；Notch1的表达阳性率在有淋巴结转移组中为41.3%，显著低于无淋巴结转移组(61.28%，P<0.05)；在其他病理特征间Notch1表达差异均无统计学意义(P>0.05)。DLL4在胃癌、癌旁和对照组中的表达阳性率分别为55.94%、45.7%和56.67%，三者间差异无统计学意义(P>0.05)；在不同病理特征间DLL4的表达差异均无统计学意义(P>0.05)。HES1在胃癌、癌旁和对照组中的表达阳性率分别为36.64%、34.40%和33.3%，三者间差异无统计学意义(P>0.05)；HES1在低分化胃癌中的表达阳性率为51.43%，高于高/中分化组(31.25%，P<0.05)；在其他病理特征间HES1的表达差异均无统计学意义(P>0.05)。Notch1、DLL4和HES1阳性组和阴性组生存期之间差异无统计学意义(P>0.05)。结论胃癌组织中Notch1呈高表达，可作为胃癌诊断和治疗的靶点；Notch1的表达与胃癌淋巴结转移呈负相关；HES1在低分化胃癌中表达升高，可能是胃癌分化程度的一个标志物。

关键词：胃癌；Notch1；DLL4；HES1；临床病理特征；生存期

DOI:10.3969/j.issn.1673-534X.2015.02.018

基金项目：甘肃省科技支撑计划(1011FKCA120)

收稿日期：(2014-07-20)

作者单位：730000兰州大学病原生物学研究所，甘肃省新药临床前研究重点实验室(何黎黎，韩俭)；730000甘肃兰州，甘肃省第二人民医院消化科(张富花，张锦华，庄剑波)；730000兰州大学病理学研究所(张建刚)

通信作者：韩俭，Email: hanj@lzu.edu.cn

Relationship between Notch1, DLL4 and HES1 expression and clinicopathologic characteristics and prognosis of gastric cancerHELi-li,HANJian.DepartmentofPathogenicBiology,SchoolofBasicMedicalSciences,KeyLabofPreclinicalStudyofNewDrugsofGansuProvince,LanzhouUniversity,Lanzhou(730000),China.ZHANGFu-hua,ZHANGJin-hua,ZHUANGJian-bo.DepartmentofGastroenterology,SecondPeople′sHospitalofGansuProvince,Lanzhou(730000),China.ZHANGJian-gang.DepartmentofPathology,SchoolofBasicMedicalSciences,LanzhouUniversity,Lanzhou(730000),China

Abstract：ObjectiveThis paper detected Notch signaling components--Notch1, DLL4 and HES1 expression in the gastric cancer and follow-up patients survival in order to analyze their relationship with clinicopathological characteristics and survival, and to explore the mechanism of gastric cancer development. MethodsGastric cancer and paracancerous tissue cases were used to manufacture tissue microarray. Immunohistochemistry was used to detect Notch1, DLL4 and HES1 expression. Patients′ survival time were followed up. The relationship between Notch1, DLL4 and HES1 expression and clinicopathological characteristics, and survival of patients were analyzed. ResultsThe Notch1 positive rate in the gastric cancer, paracancerous tissue, and control group was 48.30%, 25.00% and 16.67%, and the expression of gastric cancer group was significantly higher than that of other groups (P<0.05). The positive rate in the gastric cancer with lymph node metastasis group (41.3%) was significantly lower than that without lymph node metastasis group (61.28%) (P<0.05). The DLL4 positive rate in the gastric cancer, paracancerous tissue, and control group was 55.94%, 45.7% and 56.67% respectively, there was no significant difference between different groups (P>0.05). The HES1 positive rate in the gastric cancer, paracancerous tissue, and control group was 36.64%, 34.40% and 33.3%, and there was no significant difference between different groups (P>0.05). The HES1 positive rate (51.43%) in poorly differentiated gastric cancer was significantly higher than that in the high/middle differentiation group (P<0.05). There was no relationship between Notch1, DLL4 and HES1 expression and the patients′ survival time (P>0.05). ConclusionsGastric cancer tissues showed high expression of Notch1 which can be used as a target for gastric cancer diagnosis and treatment. Notch1 expression was negatively correlated with lymph node metastasis. HES1 expression increased in poorly differentiated gastric cancer, which may be act as an indicator of the degree of differentiation.

Key words：Gastric cancer; Notch1; DLL4; HES1; Clinicopathologic characteristic; Survival

胃癌是全球常见和高致死率的恶性肿瘤之一，2011年大约有738 000人死于胃癌[1]。胃癌的形成……