乳腺癌外周血中免疫微环境分子标志筛选研究

Breast cancer, rather than constituting a monolithic entity, comprises heterogeneous tumors with different clinical characteristics, disease courses, and responses to specific treatments. Tumor-extrinsic features, including immune microenvironment, have prognostic significance.Blood is an excellent fluid in which to find biomarkers.Our previous work have showed that blood mRNA signatures related to immune cell responses.We then investigated similarities and differences of genome-wide expression patterns between breast cancer stroma and peripheral blood mononuclear cells(PBMCs) of breast cancer patients.The data suggested that gene expression patterns of these two profilings were similar at a certain degree. PBMCs maybe a simple ,rapid and better noninvasive surrogate material for the assessment of local immune microenvironment. In this study, we will use DNA microarray data and bioinformatics tools to analysis breast cancer stroma and peripheral blood mononuclear cells(PBMCs), to further explore these presumed local and systemic influences resulting from breast cancer development. Choose common transcriptional signatures as candidate biomarkers. Then the clinical significance of these signatures will be tested in co-culture cells and clinical samples of breast cancer．These results will bring new insights into breast cancer biology and prognosis，and will show promise in predictions of clinical outcome than the traditional standards．

研究表明，免疫微环境是乳腺癌演进的重要影响因素。外周血作为微环境中免疫细胞的主要来源，也是无创诊断的理想材料，其是否能反映局部免疫微环境状态及预后诊断价值尚不明确。我们前期研究中发现不同肿瘤的外周血中差异表达的基因，其表达失调的方向显著一致且都涉及免疫和炎症功能类,同时发现乳腺癌外周血与间质微环境的基因表达模式具有相似之处。我们推测外周血中存在反映局部免疫微环境状态的分子。本课题拟利用已有的外周血和乳腺癌间质基因表达谱，首先采用计算生物学方法，从基因功能注释、通路分析、蛋白质相互作用等方面，对外周血与乳腺癌局部免疫微环境的基因表达模式作进一步分析，提取外周血中候选的免疫微环境标志分子；进而在细胞和临床样本中对候选分子的差异表达进行验证，分析其与乳腺癌局部免疫微环境的相关性，结合患者临床特征及预后确定分子标志的临床价值。以期为乳腺癌个体化治疗及预后评估提供更具临床实用性的指标。

免疫微环境是乳腺癌演进的重要影响因素。外周血作为微环境中免疫细胞的主要来源，也是无创诊断的理想材料，其是否能反映局部免疫微环境状态及诊断价值尚不明确。本研究旨在寻找更为准确、简便、实用而可重复的乳腺癌免疫微环境相关分子，用于筛选高危复发患者和指导个体化治疗提供新思路。首先采用计算生物学研究方法，评估了基因表达谱数据的可靠性和重复性。以基因之间的显著相关代替简单的重复来计数重叠基因，以及各个数据集的差异表达基因在本数据集和另一套数据集中的失调方向的一致性两个方面评估差异表达基因的一致性。通过乳腺癌组织，外周血与癌间质样本数据集，分析其基因表达模式的异同，结合基因功能注释、通路分析、蛋白质相互作用关系、文献挖掘等技术以及样本临床病例特征，对乳腺癌外周免疫与肿瘤局部免疫微环境的关系及其相互作用作了探讨，筛选出9个免疫微环境相关的候选标志分子。进一步的验证工作还在继续进行中。