基于太赫兹波谱的胰腺癌肿瘤标志物定性定量识别检测及诊断模型研究

Pancreatic cancer is an extremely malignant tumor. Early diagnosis and treatment are considered to be the key to improving the prognosis of pancreatic cancer. Tumor markers are considered as an effective means for early diagnosis of cancer. But up to now, no specific tumor marker sufficiently sensitive to pancreatic cancer has been found. Therefore, in order to improve the diagnostic accuracy of pancreatic cancer, a number of studies have adopted the method of combined detection of multiple tumor markers. However, the detection methods used in clinical and basic research currently such as chemiluminescent immunoassay（CLIA）and ELISA have many disadvantages, such as time-consuming, complex operation and high cost. Terahertz(THz) radiation lies between the microwave and infrared regions of the electromagnetic spectrum. Our previous work has proved that terahertz spectrum can qualitatively and quantitatively detect CA19-9 in human pancreatic cancer tissues, and at the same time can significantly identify cancer tissue, paracancerous tissue and normal tissue. On this basis, terahertz spectrum was used for specific identification, qualitative and quantitative detection of pancreatic cancer tumor markers, to establish a new method for detection of tumor markers that can be completed in one time, with low cost, high sensitivity and easy operation. Moreover, the mapping relationship between tumor markers such as CA19-9 and pancreatic cancer of different differentiation and stages was further explored, and the terahertz spectrum characteristics database for pancreatic cancer was established to find the rule of pancreatic cancer and build the diagnosis model of pancreatic cancer. To improve the diagnostic accuracy of pancreatic cancer, establish an interdisciplinary new method and technology platform.

胰腺癌是一种恶性程度极高的肿瘤，早诊断及早治疗是改善胰腺癌预后的关键。肿瘤标志物被认为是癌症早期诊断的有效手段。但至今未找到一种对胰腺癌足够敏感和特异的肿瘤标志物。因此，为提高胰腺癌的诊断率，多项研究采取联合检测多种肿瘤标志物的方法。但目前临床及基础研究中采取的化学发光免疫和ELISA检测方法有耗时长、操作复杂、成本高等诸多缺点。太赫兹波谱是一种介于微波和红外线之间的电磁波频谱。我们前期的工作已经证明了太赫兹波谱可以定性、定量检测人体胰腺癌组织中的CA19-9，同时可以对癌、癌旁及正常组织明显的辨识。在此基础上，利用太赫兹对胰腺癌肿瘤标志物进行特异辨识和定性、定量检测，建立一种新的一次完成多项、低成本、高灵敏度、易操作的肿瘤标志物检测方法。并进一步探寻CA19-9等肿瘤标志物与不同分化、不同分期胰腺癌的映射关系，建立对胰腺癌的太赫兹谱差异特征数据库，寻找胰腺癌癌变规律、构建胰腺癌诊断模型。

基于太赫兹光谱对癌症检测和诊断的研究日益增多，而在胰腺癌组织与相关物质的太赫兹光谱特性的研究仍处于起步阶段。利用太赫兹波谱对CA19-9等胰腺癌肿瘤标志物进行特异辨识和定性、定量检测，建立胰腺癌的太赫兹谱差异特征数据库，为提高胰腺癌诊断准确率搭建跨学科的新方法、新技术平台。. 本课题按照既定的研究目标，通过利用太赫兹波谱，进行胰腺癌肿瘤标志物定性定量识别检测研究。课题执行过程中，严格按照任务书要求，顺利完成计划任务。研究的主要内容包括实验平台的搭建、生物芯片的制备、胰腺癌细胞实际样本太赫兹测试分析及样本数据库的建立、胰腺癌样本的太赫兹成像测试、探寻潜在可应用太赫兹检测的胰腺腺鳞癌肿瘤标记物和电化学免疫传感器检测CA19-9用于太赫兹检测结果验证。. 经过三年的努力，我们成功搭建了透射式THz-TDS检测系统，并且研制了CA19-9生物芯片，建立了158例病人胰腺癌组织、癌旁组织及正常组织样本进行了太赫兹波谱检测并建立数据库。为寻找胰腺腺鳞癌特异性和敏感性更高的肿瘤标记物，我们对12例胰腺腺鳞癌进行了基因测序，发现胰腺腺鳞癌患者胚系中MAP3K1、PDE4DIP和BCR等易感基因经常发生突变。KRAS、OBSCN和HRNR的体细胞突变和USP6的胚系突变与肿瘤的侵袭和转移有关。为后续相关基因代谢产物的太赫兹检测提供了方向。我们还拓展性的使用电化学传感器来提高胰腺癌肿瘤标记物的检测结果。结果表明利用rGO，BiOCl，PtNi材料修饰到电极上制备成免疫传感器来检测目标抗原CA19-9，与传统的临床检测方法相比较，该传感器具有更好的特异性、重复性和稳定性。其结果可以进一步验证太赫兹的检测结果。

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