乳腺癌多基因甲基化与前哨淋巴结微转移预后的关系

Sentinel lymph nodes biopsy has been applied to breast cancer, the status of sentinel lymph nodes (SLNs) is one of the most important factor to prognosis and clinical therapy. But the value of sentinel lymph nodes micro-metastasis to prognostic and therapy is debated.The arguments were focused on the clinical significance of sentinel lymph nodes micro-metastasis. Based on previous research, this study will be performed to detect the clinical prognostic value of sentinel lymph nodes micro-metastasis and isolated tumor cells, analyses the relation with the survival of breast cancer patients, search the related gene methylated molecular marker, identify the association between gene methylation of SLNs metastasis and status of axillary lymph nodes, approach the feasibility of blood marker instead of tissue marker, determine the related prognostic gene of sentinel lymph nodes, make the groundwork for clinical application, in order to guide the clinical therapy.

作为一项预测乳腺癌腋窝淋巴结状态的检测手段，前哨淋巴结活检已经应用于临床，其病理诊断对预后和下一步临床治疗具有指导意义。前哨淋巴结微转移的临床意义仍有众多争议，其争议的焦点主要集中于前哨淋巴结微转移对乳腺癌患者预后的影响及对乳腺癌治疗的指导价值的评估上。本课题在既往研究的基础上，详细研究前哨淋巴结微转移和孤立的肿瘤细胞的临床预后价值，判断其与乳腺癌长期生存之间的关系，寻找与之相关的基因甲基化分子标记物，明确前哨淋巴结微转移乳腺癌基因甲基化与腋窝淋巴结状态之间的关系，探讨血液标记物代替组织检测的可行性，明确前哨淋巴结微转移相关预后基因，并奠定临床应用基础，以指导临床治疗方案。

许多前哨淋巴结阳性的乳腺癌患者并没有检测到腋窝淋巴结转移，本研究探索乳腺癌患者阳性前哨淋巴结中肿瘤分子标志物，以此来预测腋窝淋巴结转移。通过转录组分析，探索和寻找能够预测乳腺癌前哨淋巴结阳性患者腋窝转移状态的分子标志物。我们发现样本非转移组基因表达量比转移组大,且转移组之间表达基因差异大,组间共有差异表达基因160个,其中有62个表达上调的基因,98个表达下调的基因,我们还发现了一个包括12个基因的B细胞受体信号通路.在基因融合方面,腋窝转移后基因融合现象比较普遍,我们发现有14个不同基因发生融合.本研究对于进一步探索预测前哨淋巴结阳性乳腺癌患者腋窝转移状态相关的分子标志物提供了基本依据。