摘要目的：探讨胰腺癌组织及细胞中Numb与上皮细胞间质转分化相关蛋白表达的相关性及其临床病理学意义。方法收集2005年1月至2012年12月中国医科大学附属第一医院胃肠外科保存的具有完整临床资料的胰腺癌手术切除标本63例，所有患者术后病理证实均为导管腺癌。应用免疫组化方法检测63例胰腺癌标本中Numb、E钙黏蛋白（ E?cad）和波形蛋白（ Vimentin）表达情况，应用免疫印迹法和real?time PCR检测Numb、E?cad和Vimentin在胰腺癌细胞株BxPC?3和PANC?1中的表达情况。采用χ2检验及Pearson相关分析比较蛋白表达相关性及与患者临床病理学参数的关系，采用Kaplan?Meier单因素分析计算累积生存率，并行Log?Rank检验。结果免疫组化结果显示， Numb、E?cad和Vimentin在胰腺癌组织中阳性表达率分别为46?0％、41?3％和28?6％。 Numb表达与胰腺癌大小、分化程度及UICC分期呈负相关（ r＝－0?310，P＝0?010；r＝－0?359，P＝0?004；r＝－0?228， P＝0?020），E?cad表达与肿瘤分化程度呈负相关（ r＝－0?316，P＝0?012），Vimentin表达与肿瘤分化程度和淋巴结转移呈正相关（ r＝0?264，P＝0?036；r＝0?274，P＝0?030）。相关性分析结果显示，Numb表达与E?cad呈正相关（r＝0?325，P＝0?010），与Vimentin表达无相关性。单因素分析结果显示，Numb和E?cad共表达胰腺癌患者预后更好（ P＝0?046）。细胞水平免疫印迹法和real?time PCR结果显示， Numb蛋白和mRNA高表达的胰腺癌BxPC?3细胞株中E?cad高表达、Vimentin低表达；Numb蛋白和mRNA低表达的胰腺癌PANC?1细胞株中E?cad低表达、Vimentin高表达。结论 Numb和E?cad在胰腺癌组织及细胞中表达呈正相关，可能共同参与胰腺癌上皮细胞间质转分化的发生进展。

abstractsObjective To study the relationship and clinicopathological significance of Numb and epithelial?mesenchymal transition related proteins in human pancreatic cancer( PC)? Methods Sixty?three cases of pancreatic cancer tissues were obtained from department of gastrointestinal surgery in the First Hospital of China Medical University from January 2005 to December 2012, all samples were histopathologically proved to be adenocarcinoma? The expressions of Numb, E?cadherin and Vimentin proteins in 63 cases of pancreatic cancer specimens were detected by immunohistochemistry? Western blot and real?time PCR were used to examine the protein and mRNA levels in two pancreatic cancer cell lines?Pearson and chi?squared tests were used to analyze the relationship and clinicopathological characters with PC patients? Kaplan?Meier curve and log rank test were used to estimate the difference of PC patients′survival? Results The positive rates of Numb,E?cadherin and Vimentin expressions were 46?0%,41?3%and 28?6%, respectively? Numb expression was negatively associated with tumor size, differentiation and UICC stage( r=-0?310, P= 0?010;r=-0?359, P= 0?004;r=-0?228, P=0?020) , while E?cadherin expression was negatively related with tumor differentiation( r=-0?316,P=0?012)? In contrast,Vimentin expression was positively related with pancreatic cancer differentiation and lymph metastasis( r=0?264,P=0?036;r=0?274, P=0?030 )?Correlation analysis showed Numb had a positive association with E?cad expression( r= 0?325, P= 0?010 ) , but had no association with Vimentin? Moreover, patients with co?expression of Numb and E?cadherin had a significantly better overall survival in Kaplan?Meier univariate analysis(P=0?046)?Immunoblotting and real?time PCR showed that high Numb protein and mRNA levels in BxPC?3 cells were followed with high E?cadherin and low Vimentin expressions,whereas low Numb protein and mRNA levels in PANC?1 cells were followed with low E?cadherin and high Vimentin expressions, respectively? Conclusions Numb has a positive relationship with E?cadherin in both pancreatic cancer tissues and cells?The interaction between them might participate in the initiation and development of epithelial?mesenchymal transition in pancreatic cancer.