CTSD基因表遗传学修饰与乳腺癌转移的关系

目的:检测乳腺癌组织CTSD基因增强子区遗传和表遗传学改变,探讨其与乳腺癌转移的关系?方法:取152例乳腺癌标本及对应的癌旁组织,采用PCR扩增技术对CTSD基因增强子区进行扩增,产物进行基因测序?应用甲基化特异性限制性内切酶酶切联合PCR扩增技术,观察乳腺癌组织CTSD基因增强子区去甲基化状态?结果:遗传学改变研究表明,CTSD基因增强子区基因片段测序结果显示未发现有意义的突变位点?表遗传研究表明,转移乳腺癌组织中增强子区去甲基化发生率为85.3%,癌旁组织为0,两者差别有显著统计学意义(P < 0.05)?未转移乳腺癌去甲基化发生率为 51.9%,相较于癌旁组织,差别有统计学意义(P < 0.05)?转移和未转移乳腺癌去甲基化发生率相比,差别也有统计学意义(P < 0.05)?结论:CTSD基因增强子区的功能调控不受遗传学突变的影响,其去甲基化率与乳腺癌的转移有关,有望成为乳腺癌的一个预后指标?

Epigenetic modification of CTSD gene with breast cancer

Objective:To explore the relationship between genetic and epigentic modification of CTSD gene enhancer and breast cancer metastasis. Methods:CTSD gene enhancer sequence was detected in 152 cases of breast cancer specimens and paracancerous tissues using PCR amplification. CTSD gene enhancer demethylation state was observed in breast cancer by methylation-specific restriction enzyme digestion combined with PCR amplification. Results:There is no meaningful mutational site in CTSD gene enhancer sequencing. Our genetic research shows that incidence of methylation are 85.3% in metastatic breast cancer enhancer and 51.9% in non metastatic breast cancer. However no methylation is observed in paracancerous tissues. So both of the methylation incidence in metastatic and non-metastatic tissues are significantly different from that in paracancerous tissues. Conclusion:The functional regulation in CTSD gene enhancer does not suffer from the influence of genetic mutations. The demethylation incidence in CTSD enhancer is high related to metastasis of breast cancer. Therefore,demethylation level in CTSD gene enhancer may be the prognostic indicator of breast cancer.