乳腺癌是女性最常见的恶性肿瘤,其预后与癌细胞侵袭转移密切相关.但迄今为止仍未发现对乳腺癌早期诊断和转移有明确预测价值的生物标志物。Wnt信号通路在乳腺癌的发生发展及转移中起重要作用。我们前期研究发现DACT1、DACT2、PCDH10和DKK3等Wnt信号负调控因子在乳腺癌中因启动子甲基化表达下调或缺失，异常激活Wnt通路参与乳腺癌的发生及转移。但对该通路在乳腺癌的异常激活尚缺乏系统深入的研究。本项目将：系统研究乳腺癌中表达异常的Wnt/β-catenin负调控因子；其表达异常的表观遗传调控机制；这些负调控因子的甲基化状态是否与乳腺癌的临床分期、分级和激素受体状态存在相关性；是否可以单独或联合成为乳腺癌早期诊断的生物标志物或治疗及预后的评价指标。进一步深入研究Wnt/β-catenin的负调控因子在乳腺癌的发生及侵袭转移的作用和机制，有望筛选出潜在的乳腺癌诊断标志物和/或治疗靶点。

Breast cancer is the most common female malignant tumor，and the prognosis of breast cancer is closely related to invasion and metastasis。However, until now no explicit certificated molecular markers with high sensitivity and specificity have been found that could tangibly predict breast cancer invasion and metastasis, and there is no specific biological target therapies against it . Wnt/β-catenin signaling pathway plays an important role in the progression，invasion and metastasis of breast cancer . Previous studies have found that PACT1,PACT2,PCDH10,DKK2,DKK3 and other factors function as negative regulators of Wnt/β-catenin signaling pathway, and are downregulated or silenced by promoter methylation, aberrantly activating Wnt/β-catenin pathway and participating in progression, invasion and metastasis of breast cancer. Our project aims to systematically study the aberrant expression of negative regulatory factors of Wnt/β-catenin pathway in breast cancer, it’s epigenetic regulation mechanism of aberrant expression and whether methylation status is the main way of aberrant regulation. Whether the methylation status of these negative regulatory factors correlate with clinical stage, grade and hormone receptor status of breast cancer. Whether these factors could alone or in combination to be early diagnostic markers and to be assessment criteria of treatment and prognosis. Further study the mechanism of the negative regulatory factor Wnt/β-catenin pathway in the occurrence ,metastasis and invasion of breast cancer, is also expected to screening potential marker for breast cancer diagnosis or therapeutic target.