前列腺癌诊疗已达到新瓶颈，探索新诊断标记物和治疗靶点是突破瓶颈关键。基于对前列腺癌鼠模型的差异蛋白质表达图谱和建立代谢途径网络分析显示前列腺癌PDGFs通路成员在前列腺癌组织中表达显著增高，PDGF-C有望成为前列腺癌新的生物学标记和治疗靶点。课题研究内容： 1）基于蛋白质组学和知识挖掘技术技术，确立和验证新信号途径的分子靶点2）构建PDGF-C基因敲除的前列腺癌动物模型，通过动态分子影像技术进一步验证新的蛋白靶点在信号通路中的生物学作用。根据PDGFs和相关节点蛋白在前列腺癌发展中的动态可视化信息，为以PDGF为靶向的抗癌药物提供理论依据和评价手段。

To investigate new diagnostics marker and therapy targets for prostate cancer (PC) have been current key issues in PC clinical research since it has been a bottleneck for years. Our studies of differential proteomics research revealed that PDGF signaling pathway is involved in PC early development, however, the detailed target and mechanism is still keeping concern. This study intends to 1) perform a complete proteome expression profiling on biopsy and identify novel biomarkers by knowledge mining pathway analysis； 2) construct the prostate cancer mouse model with PDGF-C gene knock-out, and verify the biological function of the new protein target in the signal pathway by dynamic molecular imaging technology. According to the dynamic visualization information of PDGFs and related proteins in the development of prostate cancer, we will provide the theoretical basis and evaluation means for PDGF-targeted anticancer drugs.

前列腺癌的早期诊断能够显著提高患者的存活率，因而探索新诊断标记物和治疗靶点意义重大。PDGFs信号通路是前列腺癌代谢途径网络中的重要成员之一，血小板衍生生长因子B（Platelet-derived growth factor, PDGF-B）在其中起重要作用。本研究通过高分辨率高灵敏度质谱，对来自在前列腺癌小鼠和正常野生小鼠的前列腺组织样品进行了蛋白质组学分析，鉴定特异性蛋白，并在此基础上筛选出具有显著统计学差异的蛋白共计52种。同时，发现其中18种蛋白受PDGF-B调控。其中，PDGF-B及其所调控的PDIA3、PRDX2及HNRNPL在大多数标本中的肿瘤区域都呈现出明显的高表达。这为前列腺癌治疗新靶点的发展提供了思路。基于以上蛋白质组学分析，本研究进一步构建基于磁共振分子影像的靶向探针，建立基于PDGF-B以及相关节点蛋白的靶向抗癌治疗体系。