前列腺癌PIA－PIN－PCa恶性转化的免疫调控网络及其分子机制研究

炎性微环境中的免疫细胞及其因子在前列腺癌的发生发展中具有重要作用，但其对PIA-PIN-PCa恶性转化的作用机制和调控网络尚未明了。本研究采用激光捕获显微切割技术在同一肿瘤样本中分别提取和建立PIA、PIN、PCa细胞的RNA文库，采用高通量转录组测序并应用生物信息学等方法进行比对分析，建立差异表达谱。还将进一步分析炎性细胞与肿瘤细胞之间免疫调控相关因子的异同，建立共调控网络；同时对转录组和蛋白差异谱进行对比及聚类分析，以精确分析炎症微环境中免疫调控因子的作用。本研究将以炎症－免疫－肿瘤为主线，以炎性微环境中巨噬细胞作为主要研究对象，以PIA-PIN-PCa疾病过程作为模板，以基因组学及非编码转录基因组学为技术手段，用高通量生物信息学方法揭示“PIA-PIN-PCa”恶性转化的动态免疫调控网络。还将应用免疫与生物学方法进行人工干预调控网络，以验证免疫调控网络在临床诊断及治疗上的意义。

Inflammatory microenviroment is a critical factor in the development and prograss of the prostate cancer (PCa), however, the regulatory pathways are yet fully understood. This study aims to explore the immunoregulatory pathways during the development from proliferative inflammatory atrophy (PIA) to prostate intraepithelial neoplasia (PIN) and PCa. We will apply a newly developed technology, called LCM, to selectively isolate RNAs from the same clinical sample so that we are able to campare the differences of regulatory pathways among PIA, PIN and PCa concourrently using high throughput sequencing and bioinformatives. We will further investigate differential expression of the immune cells, such as tumor associated macrophages (ATM) and subpubulations (eg., M1 vs M2), in order to define the key molecules in the immunoregulatory networks in the PIA, PIN and PCa tissues. Finally, we will confirm the regulatory pathways and the key molecules involved in the PIA-PIN-PCa using in vitro co-culture system, as well as siRNA-based therapy in a murine prostate cancer model.