结直肠癌中Ets-1和整合素α6β4的表达及临床意义

  • 摘要: 目的:检测结直肠癌中转录因子Ets-1和整合素α6β4的表达,探讨其在结直肠癌浸润转移中的作用及临床意义。方法:选取2007年6月至2008年6月间天津医科大学总医院外科40例结直肠癌手术标本为研究对象,分别采用荧光实时定量PCR和免疫组织化学方法检测肿瘤和切端组织中Ets-1和整合素α6β4的mRNA和蛋白表达水平,并结合临床病理资料进行统计学分析。结果:Ets-1和整合素α6β4在肿瘤组织中的mRNA表达水平和蛋白表达水平均高于切端组织 (P<0.05);Ets-1 mRNA的表达与肿瘤的组织学类型、肿瘤部位、大小及分化程度未见相关性 (P>0.05),伴淋巴结转移者Ets-1 mRNA的表达明显高于不伴淋巴结转移者, 其差异具有统计学意义 (P<0.05), Ets-1 mRNA表达与大肠癌浸润深度及Dukes分期存在正相关, 伴随肿瘤浸润深度和临床分期的增加, Ets-1 mRNA表达明显增加, 其差异有统计学意义 (P<0.05); 淋巴结转移者的Ets-1蛋白阳性率为91.3% (21/23),无淋巴结转移者为58.8% (10/17),两者差异具有统计学意义 (P<0.05),伴随肿瘤浸润深度和Dukes分期的增加, 肿瘤组织中Ets-1蛋白阳性率也显著增加 (P<0.05), 而Ets-1蛋白表达水平与病理类型及分化程度未见相关性 (P>0.05); 结直肠癌中Ets-1的表达与整合素α6β4的表达呈正相关 (P<0.05)。结论: 检测结直肠癌内Ets-1和整合素α6β4的表达可作为评价肿瘤侵袭转移、 判断预后的重要指标, Ets-1可能成为结直肠癌基因治疗新的靶点。

     

    Abstract: Expression of Ets-1 and Integrin α6β4 and Its Clinical Significance in Colorectal CarcinomaChengmei ZHAO1,2, Gang KIU1, Yujie QIU1, Liwei ZHU11Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China2Tianjin Medical, Tianjin 300222, ChinaCorrespondence to: Liwei ZHU, E-mail: zhuliwei0804@126.comAbstract Objective: To detect the expression of Ets-1 and integrin α6β4 in colorectal carcinoma ( CRC ), and to explore therole and clinical significance of these transcription factors in the invasion and metastasis of CRC. Methods: Surgical specimens from40 CRC patients were used in this study. The mRNA and protein levels of Ets-1 and integrin α6β4 in CRC tissue and the surgical mar-ginal zone were assayed using real-time quantitative PCR and immunohistochemical methods. Statistical analysis for the results of theassay and clinicopathologic data was conducted. Results: Both mRNA and protein expression of Ets-1 and integrin α6β4 were signifi-cantly higher in CRC tissue than in the marginal zones ( P < 0.05 ). There was no correlation among the Ets-1 mRNA expression, histo-logical type, location, size of the CRC, or the extent of differentiation ( P > 0.05 ). The level of Ets-1 mRNA expression was significant-ly higher in the cases with positive lymph nodes than in the cases with negative nodes. There were significant differences between thetwo groups ( P < 0.05 ). There was a positive correlation among the expression of Ets-1 mRNA, depth of CRC infiltration and Duke’ sstaging ( P < 0.05 ). The positive rate of Ets-1 protein detection was 91.3% ( 21/23 cases ) in the cases with nodal metastasis and 58.8%( 10/17 cases ) in the cases without nodal metastasis. There were significant differences between the two groups ( P < 0.05 ). There wasa significant increase in the positive rate of Ets-1 protein in CRC, with a corresponding increase in tumor invasion depth and Duke'sstaging ( P < 0.05 ). Integrin α6β4 protein expression was similar to that of ETS-1. No relationship was detected between integrin α6β4expression and pathologic type or extent of tumor differentiation ( P < 0.05 ). A positive correlation between Ets-1 and integrin α6β4 inCRC was confirmed ( P < 0.05 ). Conclusion: Ets-1 and integrin α6β4 expression in CRC may be an important factor in metastasis anddetection of these proteins may assist in determining prognosis. Ets-1 may become a new target for gene therapy of CRC.Keywords Ets-1; Integrin α6β4; Colorectal carcinoma

     

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