血浆D-dimer检测恶性肿瘤血行微转移的临床价值评估及机制研究

项目名称： 血浆D-dimer检测恶性肿瘤血行微转移的临床价值评估及机制研究

项目编号： No.81501826

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刁冬梅

作者单位： 西安交通大学

项目金额： 18万元

中文摘要： 血行微转移是肿瘤治疗失败的主要原因，循环肿瘤细胞（CTCs）异质性导致目前检测手段存在缺陷。我们前期研究发现血浆D-dimer与血行转移关系密切，且与CTCs检测正相关；基质金属蛋白酶MT1-MMP可能是影响CTCs作用微环境产生D-dimer的重要原因。我们假设，肿瘤患者血浆D-dimer升高与CTCs形成的微血栓有关，是CTCs作用机体微环境产生的关键伴随物，可用于检测血行微转移。本实验拟通过临床检测评价D-dimer诊断血行转移的价值、体内外实验揭示其升高机制。通过Cellsearch®-CTC等检测患者血液标本并随访比较其诊断效率；建立血行转移模型并检测D-dimer的变化，利用蛋白抗体芯片筛选与MT1-MMP作用导致D-dimer改变的相关因子，绘制网络图并验证。D-dimer作为一种无创、廉价、快速的检测方法，拟通过本研究为它在恶性肿瘤血行微转移及常规筛查方面的应用提供依据。

中文关键词： 转化医学；D-dimer；循环肿瘤细胞；微转移

英文摘要： Metastasis remains the major cause of cancer treatment failure, Circulating Tumor Cells(CTCs) heterogeneity has limited the clinical application of traditional methods. In our previous study, we found plasma D-dimer levels elevated in metastasis caner patients and showed a linear association with CTCs. Additionally, expression of MT1-MMP in CTCs may play an essential role in D-dimer generating in microenvironment. So we hypothesize that plasma D-dimer levels are elevated after CTCs clot formation and is an essential accompaniment of CTCs, it can be used to identify patients with micro-hematogenous metastasis. Based on previous studies, we designed this multiple-part experimental study to explore the effectiveness of managing suspected metastasis using plasma D-dimer testing in clinical cancer patients, and found the related mechanism in vivo, also by bioinformatics technology. In this study, we will collect blood and tissue samples from cancer patients with a follow-up study to evaluated the clinical use of D-dimer in detecting hematogenous metastasis and compared with Cellsearch®CTC method. Then, we will construct in vivo hematogenous metastasis model after transfect p-EGFP vector to B16/F10 melanoma cells and other tumor cells, thereafter, we will detect the change of plasma D-dimer levels in micro-hematogenous metastasis model. Additional, we will explore related mechanism of D-dimer generating by MT1-MMP though protein microarry technology and prove it. The propose of this study is to identify a factor which is not only effective but also rapid, ease of measurement, non-invasion and the low cost for predict micro-metastasis in cancer patients.

英文关键词： translational research;D-dimer;circulating tumor cells;micro-metastasis