Notch1和PTEN在胃癌组织中的表达及其意义

Expression and Significance of Notch1 and PTEN in Gastric Cancer

背景与目的:Notch1属于Notch跨膜受体家族,在细胞分化中发挥关键作用。最近研究发现Notch1具有促癌和抑癌双重作用,在肿瘤发生机制中作用复杂,在胃癌组织中的表达以及与临床病理特征的关系目前尚不清楚。本研究旨在研究Notch1与PTEN在胃癌组织中的表达及其意义。方法:通过免疫组化方法检测168例胃癌组织和27例正常胃组织的组织芯片中Notch1和PTEN的表达,分析两者的表达水平与临床病理特征的关系以及两者的相互关系。结果:Notch1在胃癌组织中的阳性率为61.9%(104/168),明显高于正常胃组织25.9%(7/27)(P<0.05),其表达与肿瘤大小、分化程度、浸润深度及脉管浸润的相关性均有统计学意义(P<0.05)。PTEN在胃癌组织中的阳性率为47.0%(79/168),明显低于正常胃组织92.6%(25/27)(P<0.01),且与肿瘤大小、分化程度、浸润深度、脉管浸润、淋巴结转移和远处转移的相关性均有统计学意(P<0.05)。Notch1和PTEN的表达呈负相关(r=-0.170,P<0.05)。Kaplan-Meier分析显示,Notch1阴性组3年生存率为78.0%,显著高于阳性组的34.0%(P<0.01);PTEN阴性组3年生存率为38.0%,显著低于阳性组的62.0%(P<0.01)。Cox回归多因素分析显示Notch1表达是一个独立预后因素。结论:Notch1与PTEN的表达失调可能与胃癌的发生发展相关。Notch1表达可作为评价胃癌预后的指标。

BACKGROUND ＆ OBJECTIVE： Notch homolog 1 （Notch1） belongs to the Notch family of transmembrane receptors and plays an important role in cell differentiation. Notch1 plays a profound role in carcinogenesis and can be both oncogenic and tumor suppressive. However, the correlation of Notch1 expression to clinicopathologic features of gastric cancer is unclear. This study was to investigate the expression and significance of Notch1 and PTEN in gastric cancer. METHODS. The expression of Notch1 and PTEN in a tissue microarray containing 168 spots of gastric cancer tissue and 27 spots of normal gastric tissue was detected by SP immunohistochemistry. The correlation of Notch1 expression to PTEN expression, and their correlations to the clinicophathologic features of gastric cancer were analyzed. RESULTS： The positive rate of Notch1 was significantly higher in gastric cancer than in normal gastric tissue （61.9% vs. 25.9%, P〈0.05）, and closely related to tumor size （P〈0.01）, differentiation grade （P〈0.01）, depth of invasion （P〈0.01） and vessel invasion （P〈0.05）. The positive rate of PTEN was significantly lower in gastric cancer than in normal gastric tissue （47.0% vs. 92.6%, P〈0.01 ）, and related to tumor size （P〈0.01）, differentiation grade （P〈0.05）, depth of invasion （P〈0.01）, vessel invasion （P〈0.05）, lymph node metastasis （P〈0.05） and distant metastasis （P〈0.05）. The expression of Notch1 was negatively correlated to that of PTEN （r=-0.170, P〈0.05）. The 3-year survival rate was significantly higher in Notchl-negative patients than in Notchl-positive patients （78.0% vs. 34.0%, P〈0.01）, and was significantly higher in PTEN-positive patients than in PTEN-negative patients （62.0% vs.38.0%, P〈0.01）. COX regression analysis showed that Notch1 expression was an independent prognostic factor of gastric cancer. CONCLUSIONS： The dys-regulation of PTEN and Notch1 expression may correlate to the occurrence and development of gastric cancer. Notch1 may be a novel prognostic marker of gastric cancer.