胆管癌组织中microRNA21的表达与上皮间质转化的关系及对预后评估的价值

Expression of microRNA -21 in cholangiocarcinoma tissues and its relation with epithelial mesenchymal transition

    摘要
  • 摘要:
    目的 研究microRNA-21在胆管癌组织中的表达及其与上皮间质转化(EMT)和患者预后的关系。
    方法 收集2005年1月至2010年1月安徽医科大学附属省立医院手术切除的41例胆管癌标本及10例行胆管癌根治术患者的癌旁组织标本，分别采用原位杂交和免疫组织化学法检测microRNA-21以及EMT相关标志蛋白E-cadherin、N-cadherin的表达，并分析microRNA-21与EMT的关系以及microRNA-21的表达对临床预后评估的价值。计数资料采用χ2检验，相关性分析用Spearman法，采用Kaplan-Meier法绘制生存曲线，生存分析采用Log-rank检验。
    结果 胆管癌组织中microRNA〖KG*9〗21的阳性表达率为63%，高于癌旁组织的30%，两者比较，差异有统计学意义(χ2=0.324，P<0.05)；microRNA-21的表达与肿瘤细胞分化程度、有无淋巴结转移、有无神经和(或)脉管浸润密切相关(χ2=6.365，0.552，11.896，P<0.05)，但与患者性别、年龄、肿瘤位置、病理类型无明显相关(χ2=0.322，0.588，0.510，0.256，P>0.05)。E-cadherin与N-cadherin的表达分别与有无淋巴结转移、有无神经和(或)脉管浸润相关(χ2=4.630，5.512；6.600，7.152，P<0.05)，但与患者的性别、年龄、肿瘤位置、肿瘤细胞分化程度及病理类型无明显相关(χ2=0.266，0.013，0.067，0.666，0.003；1.036，0.997，1.808，2.997，0.812，P>0.05)。同一批胆管癌组织中microRNA-21表达与EMT相关标志蛋白E-cadherin、N-cadherin的表达具有相关性(r=0.373，0.614，P<0.05)。术后生存分析结果显示：microRNA-21低表达者总体生存率及无瘤生存率均高于microRNA-21高表达者，两者比较，差异有统计学意义(χ2=3.999，4.376，P<0.05)。
    结论 microRNA-21在胆管癌组织及转移淋巴结中高表达，可能通过诱导EMT的发生来促进胆管癌的浸润和转移；microRNA-21可以反映患者的预后。

     

    Abstract:
    Objective  To investigate the expressions of microRNA-21 in cholangiocarcinoma tissues and the relationship between epithelial mesenchymal transition (EMT) and the prognosis of patients.
    Methods  Forty-one samples of cholangiocarcinoma and 10 samples of adjacent tissues from 10 patients who received radical resection of cholangiocarcinoma at the Provincial Hospital of Anhui Medical University from January 2005 to January 2010 were collected. The expressions of microRNA-21, E-cadherin and N-cadherin were detected by in situ hybridization and immunohistochemistry, and effect of their expressions on the prognosis was analyzed. Enumeration data were analyzed using chisquare test. The correlation between microRNA-21 and EMT markers was analyzed using the Spearman correlation coefficient. The survival curve was drawn by KaplanMeier method, and the survival rate was analyzed using the Log-rank test.
    Results  The expression rate of microRNA-21 in the cholangiocarcinoma tissues was 63%, which was significantly higher than 30% of that in the adjacent tissues (χ2=0.324, P<0.05). The expression of microRNA-21 was closely related with the tumor differentiation degree, lymph node metastasis, perineural invasion (χ2=6.365, 0.552, 11.896, P<0.05), but not with gender, age, tumor location and tumor type (χ2=0.322, 0.588, 0.510, 0.256, P>0.05). The expressions of Ecadherin and Ncadherin were related with lymph node metastasis and perineural invasion (χ2=4.630, 5.512; 6.600, 7.152, P<0.05), but not with gender, age, tumor location, tumor differentiation degree and tumor type
     (χ2=0.266, 0.013, 0.067, 0.666, 0.003; 1.036, 0.997, 1.808, 2.997, 0.812, P>0.05). A positive correlation between the expression of microRNA-21 and EMT related markers E-cadherin and N-cadherin was detected (r=0.373, 0.614, P<0.05). The results of survival analysis showed that the overall survival rate and tumor-free survival rate of patients with low expression of microRNA-21 were significantly higher than those of high expression of microRNA-21 (χ2=3.999, 4.376, P<0.05).
    Conclusion  Over expression of microRNA-21 in cholangiocarcinoma and metastatic lymph nodes may accelerate the invasion and metastasis of cholangiocarcinoma through inducing EMT, microRNA-21 might predict the prognosis of patients.

     

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