乳腺癌的复发和转移缺乏有效的早期诊查手段，致使治疗费用高却预后差，是其导致死亡的主因。因此，寻找新型肿瘤标志物对于早期诊断乳腺癌的复发和转移及尽早治疗至关重要。研究证实miRNA在乳腺癌发生和进展中发挥重要作用，其在血清中表达稳定，并具有特异性强、灵敏度高等特点，完全可能成为新型分子标志物。本课题拟采用Solexa测序技术与基于Taqman探针的实时荧光定量PCR技术相结合，筛选出复发和转移性乳腺癌患者血清中特异性变化的miRNA，结合患者的临床资料和随访数据进行统计学分析，建立复发和转移性乳腺癌的血清miRNA表达的指纹图谱，探寻miRNA在乳腺癌复发和转移的早期诊断、预后判断、疗效分析、随访监测等方面的应用。本研究不仅对转移和复发性乳腺癌的临床诊治意义重大，而且能够带来巨大社会和经济效益，具有广阔的临床应用前景。

Recurrent and metastatic breast cancer which accompanied by high cost and poor prognosis is the leading cause of death due to a lack of effective means of early detection. Identifying novel biomarkers is vital for early detection and treatment of recurrent and metastatic breast cancer. Evidences show that miRNA is essential in the development and progression of breat cancer, and make great promise as novel markers for their stable expression, specificity and high sensitivity. This study will screen specifically changed serum miRNA in recurrent and metastatic breast cancer patients by Solexa and real-time PCR, and identify the serum miRNA fingerprint in combination with the clinical and follow-up data, in an effort to explore the application of the miRNAs in the diagnosis of recurrence and metastasis, prognosis, and treatment analysis and follow-up monitoring of breast cancer. Therefore, this study will provide insights for diagnosis and treatment of recurrent and metastatic breast cancer with great value and potential social and economic benefits.

利用Solexa测序技术与基于Taqman探针的实时荧光定量PCR技术相结合，筛选出复发和转移性乳腺癌患者血清中特异性变化的miRNA，并证实血清miRNA在乳腺癌复发和转移中发挥重要作用，其中miR-31（上升）、miR-21（上升）、miR-125b（下降）、miR-34（下降）、miR-194（下降）及let-7g（下降）等有显著差异。结合患者的临床资料和随访数据进行统计学分析，建立复发和转移性乳腺癌的血清miRNA表达的指纹图谱，探寻miRNA在乳腺癌复发和转移的早期诊断、预后判断、疗效分析、随访监测等方面的应用。本研究不仅对转移和复发性乳腺癌的临床诊治意义重大，而且能够带来巨大社会和经济效益，具有广阔的临床应用前景。本基金共发表SCI论文4篇，国内学术杂志上发表核心期刊文章2篇，培养硕士研究生5名。