肝胆胰外科杂志 ›› 2019, Vol. 31 ›› Issue (5): 277-282.doi: 10.11952/j.issn.1007-1954.2019.05.005

• 胰腺肿瘤的诊治 • 上一篇    下一篇

FOXA2在胰腺癌组织中的表达及其对胰腺癌细胞增殖和侵袭的影响

赵金磊,季春勇,罗红杰,刘东亮    

  1. 郑州大学附属郑州市中心医院   肝胆胰微创外科,河南   郑州   453000
  • 收稿日期:2018-12-20 出版日期:2019-05-22 发布日期:2019-05-22
  • 通讯作者: 季春勇,主任医师,E-mail:13603716558@163.com。
  • 作者简介:赵金磊(1981-),男,河南周口人,住院医师,硕士。

Expression of FoXA2 in pancreatic carcinoma and its effects on proliferation and invasiveness of pancreatic carcinoma cells 

ZHAO Jin-lei, JI Chun-yong, LUO Hong-jie, LIU Dong-liang   

  1. Department of Hepatobiliary and Pancreatic Minimally Invasive Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 453000, China 
  • Received:2018-12-20 Online:2019-05-22 Published:2019-05-22

摘要:

目的 探讨FOXA2在胰腺癌组织中的表达,以及特异性沉默FOXA2基因表达对PANC-1细胞 增殖、迁移和侵袭能力的影响。方法 选取2010年1月至2013年1月在郑州市中心医院择期行手术切除的 胰腺癌患者71例,所有患者从手术时间开始进行随访,截止时间为2018年1月31日或患者死亡时间,采用免疫组化SP法检测胰腺癌和癌旁组织中FOXA2蛋白表达,生存分析采用Kaplan-Meier法和Log-Rank检 验,影响患者预后的危险因素分析采用Cox比例风险回归模型。培养人胰腺癌PANC-1细胞,分为siRNAFOXA2组、siRNA-NC组和对照组,实时荧光定量PCR技术和Western blotting法检测细胞中FOXA2 mRNA和蛋白表达,CCK-8法检测细胞增殖活性,Transwell法检测细胞迁移和侵袭能力。结果 胰腺癌组 织中FOXA2蛋白阳性表达率(32.39%)低于癌旁组织(83.10%,P<0.001);胰腺癌组织中FOXA2蛋白阳性 表达与TNM分期、淋巴结转移及脉管癌栓有关(P<0.05);Kaplan-Meier生存分析结果显示,阳性组患者平 均生存时间高于阴性组,Log-Rank检验差异有统计学意义(χ2=11.135,P=0.001);Cox比例风险回归模型 结果显示,淋巴结转移、脉管癌栓和FOXA2蛋白阴性表达是影响患者预后的风险因素(P<0.05);siRNAFOXA2组细胞中FOXA2 mRNA和蛋白表达量低于siRNA-NC组和对照组(P<0.05);siRNA-FOXA2组24 h、 48 h、72 h和96 h时OD值均高于siRNA-NC组和对照组(P<0.05);siRNA-FOXA2组PANC-1和AsPC-1细胞 中迁移细胞数和侵袭细胞数均高于siRNA-NC组和对照组(P<0.05)。 结论 胰腺癌组织中FOXA2蛋白呈 低表达,是影响患者预后的风险因素;沉默FOXA2后会促进胰腺癌细胞增殖、迁移和侵袭。 

关键词: 胰腺癌, 叉头框蛋白A2(FOXA2), 细胞迁移, 细胞侵袭

Abstract:

objective  To investigate the expression of FOXA2 in pancreatic carcinoma, and to explore the effects of specific silencing of FOXA2 gene expression on the proliferation, migration and invasion of PANC1 cells. Methods  A total of 71 cases of patients with pancreatic carcinoma underwent elective surgical resection in Zhengzhou Central Hospital were selected from Jan. 2010 to Jan. 2013. All patients were followed-up from the time of surgery treatment, and the deadline was Jan. 31, 2018 or the time of death. Immunohistochemical SP method was used to detect the expressions of FOXA2 proteins in pancreatic carcinoma and adjacent tissues. Kaplan-Meier method and Log-Rank test was used for survival analysis. Cox proportional risk regression model was used to analysis the risk factors that affect patient prognosis. Human pancreatic carcinoma PANC1 cells were cultured and divided into siRNA-FOXA2 group, siRNA-NC group and control group. Real-time fluorescence quantitative PCR and Western blotting were used to detect the expressions of FOXA2 mRNA and protein in cells. CCK-8 assay was used to detect cell proliferation activity. Transwell assay was used to detect cell migration and cell invasion. Results  The positive expression rate of FOXA2 protein in pancreatic carcinoma tissues was 32.39%, which was lower than that in adjacent tissues (83.1%, P<0.001). The positive expression of FOXA2 protein in pancreatic carcinoma was related to TNM stage, lymph node metastasis and vascular tumor embolus (P<0.05). Kaplan-Meier survival analysis showed that the average survival time in the positive group was higher than that in the negative group, the Log-Rank test showed that the difference was statistically significant (χ2=11.135, P=0.001). Cox proportional hazards regression model results showed that lymph node metastasis, vascular tumor embolus, and negative expression of FOXA2 protein were risk factors that affecting patient prognosis (P<0.05). The expression levels of FOXA2 mRNA and protein in the siRNA-FOXA2 group were lower than those in the siRNA-NC group and the control group (P<0.05). The OD values at 24 h, 48 h, 72 h and 96 h in the siRNA-FOXA2 group were higher than those in the siRNA-NC group and the control group (P<0.05). The number of migrating cells and the number of invasive cells in the siRNA-FOXA2 group were higher than those in the siRNA-NC group and the control group (P<0.05). Conclusion  The expression of FOXA2 protein in pancreatic carcinoma tissues is low, which is a risk factor influencing prognosis. Silencing of FOXA2 expression can promote proliferation, migration and invasion of pancreatic cancer cells. 

Key words: pancreatic carcinoma, forkhead box A2(FOXA2), cell migration, cell invasion

中图分类号: 

  • R735.9 
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