乳腺癌WIF-1基因表达及其临床病理特征与该基因启动子区域甲基化的关联

Correlation of WIF-1 expression and clinicopathologic significance in breast cancer with aberrant DNA methylation

  • 摘要:
      目的  研究WIF-1(Wnt inhibitory factor-1)mRNA在乳腺癌组织中的表达及其启动子区域甲基化情况,进一步探讨WIF-1基因甲基化与乳腺癌临床病理特征的关系。
      方法  收集2009年9月1日至2009年12月30日青岛大学附属医院乳腺外科手术切除新鲜组织标本69例,其中良性病变组织9例,乳腺癌及癌旁组织各30例,应用RT-PCR及甲基化特异性PCR(methylation specific PCR,MSP)检测乳腺癌组织、相应癌旁组织和乳腺良性病变组织中WIF-1mRNA表达及其启动子甲基化情况。
      结果   癌组织中WIF-1基因表达率明显低于相应癌旁组织及乳腺良性病变组织,具有显著性差异(χ2=41.786,P < 0.05);与其他两组相比甲基化率在癌组织中明显升高(矫正χ2=16.484,P < 0.05);WIF-1基因表达下降与其异常甲基化存在明显关联(P=0.023);WIF-1异常甲基化与乳腺癌发病年龄、肿瘤分级、组织分型和淋巴结转移无相关性(P>0.05)。
      结论  异常甲基化可能是乳腺癌WIF-1基因表达下降的重要原因,是乳腺癌发生、发展的重要机制。

     

    Abstract:
      Objective   To investigate the mRNA expression of the WIF-1 gene and the methylation of its promoter in breast cancer, and to determine the correlation between the epigenetic aberrant WIF-1 DNA methylation and the clinicopathological significance of WIF-1 in breast cancer.
      Methods  RT-PCR and sensitive methylation-specific-PCR (MSP) were used to detect WIF-1 mRNA expression and the methylation of the WIF-1 promoter in 30 breast cancer samples as well as in tumor-adjacent tissue samples and 9 benign breast tissues.
      Results   The WIF-1 mRNA expression in 30 breast cancer samples significantly decreased compared with those of the other two groups. In addition, WIF-1 methylation was more frequent in breast-tumor tissues compared with those in tumor-free tissues. Meanwhile, WIF-1 mRNA expression in breast cancer tissues involved the abnormal methylation of its promoter. Clinicopathological correlation analysis showed that the abnormal methylation of the WIF-1 gene promoter was not associated with age, TNM stage, histotype, or lymph node metastasis.
      Conclusion   WIF-1 mRNA expression loss due to abnormal methylation may be a crucial factor in breast cancer development and can thus be used in the prognosis and progression of the disease.

     

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