基于肿瘤干细胞源性外泌体(exosomes)的血液活检在胰腺癌早期诊断及预后评估中的应用研究

Difficulty of early diagnosis and early occurrence of metastasis are the main reasons for the high mortality rate of pancreatic cancer (PaCa). At present, there is lack of effective clinical indicators. Research shows that tumor-derived exosomes, which had been present in the blood in the early stage of tumor formation and before metastasis, is the vanguard forces of tumor formation and metastasis; Cancer stem cell-derived exosomes (CSC-Exos) has stronger migration ability, so the detection of blood CSC-Exos for early diagnosis and monitoring of progress for PaCa has great research potential and the value of application. On the basis of previous work, this project intends to detect the proportion of expression of pancreatic cancer stem cells (Pa-CSCs) specific surface protein positive exosomes in serum by flow cytometry and compare the differences among the experimental group (PaCa patients), control group (benign tumors of the pancreas, chronic pancreatitis) and blank control group (healthy people), analyse the relationship of the CSC-Exos level to metastasis and to the tumor load of pre and post operation combined with the test results and clinical data, and explore the application value of blood biopsy based on CSC-Exos for early diagnosis and prognostic evaluation of PaCa, to provide new ideas and new targets for the prevention and treatment of PaCa.

早期诊断困难、早期发生转移是胰腺癌(PaCa)死亡率高的主要原因，目前尚缺乏有效的临床检测指标。研究表明，肿瘤细胞分泌的exosomes是肿瘤形成和转移的先锋部队，在肿瘤形成早期和转移灶形成前已存在于血液中；肿瘤干细胞分泌的exosomes(CSC-Exos)具有更强的迁移能力，因此检测血液中CSC-Exos对于PaCa早期诊断和进展监测具有较大的研究潜力和应用价值。本课题在前期工作的基础上拟采用流式细胞仪检测比较血清胰腺癌干细胞(Pa-CSCs)特异表面蛋白阳性exosomes所占比例在实验组(PaCa患者)与条件对照组(胰腺良性肿瘤、慢性胰腺炎患者)和空白对照组(健康人群)之间的差异，结合检测结果及临床资料，分析CSC-Exos含量与转移、手术前后肿瘤负荷的关系，探索基于CSC-Exos的血液活检用于PaCa早期诊断及预后评估的应用价值，为PaCa的防治提供新思路和新靶点。

早期诊断困难、早期发生转移是胰腺癌(PaCa)死亡率高的主要原因，目前尚缺乏有效的临床检测指标。研究表明，肿瘤细胞分泌的exosomes是肿瘤形成和转移的先锋部队，在肿瘤形成早期和转移灶形成前已存在于血液中；肿瘤干细胞分泌的exosomes(CSC-Exos)具有更强的迁移能力，因此检测血液中CSC-Exos对于PaCa早期诊断和进展监测具有较大的研究潜力和应用价值。本课题在前期工作的基础上拟采用流式细胞仪检测比较血浆胰腺癌干细胞(Pa-CSCs)特异表面蛋白阳性exosomes所占比例在实验组(PaCa患者)与条件对照组(胰腺良性肿瘤、慢性胰腺炎患者)和空白对照组(健康人群)之间的差异，结合检测结果及临床资料，显示Epcam+ Exos可作为胰腺癌的早期诊断标志物，Tspan8+ Exos和CD44v6+ Exos可作为胰腺癌发生远处转移的预测标志物，其研究结果具有较大的临床应用和科研转化价值。