基于尿液肿瘤标志物SERS与SEROA光谱技术的食道癌筛查研究

Esophageal cancer is a kind of gastrointestinal tumor with very high fatality rate and China is the high-incidence areas of esophageal cancer in the world-wide, so there is urgent need to develop early noninvasive detection methods for esophageal cancer diagnosis in our country. Urine can carry some kinds of tumor markers that can be sensitive response to tumor existence and development, but its concentration is very low and extremely hard to detect. The big advantage of surface enhanced Raman spectroscopy (SERS) is the extremely high detection sensitivity, which is particularly suitable for detection of the low concentration tumor marker.Surface enhanced Raman optical activity (SEROA) spectrum can deeply reflect the advanced molecule structural information by the interaction between the chiral molecule and laser. It is the first time that we use SERS and SEROA technology to do detection especially for the tumor marker of urine protein and modified nucleoside, which can eliminate the interference of exogenous substances and enhance the Raman signal of tumor marker as much as possible. Meanwhile, we take advantage of a variety of statistical methods to analyze spectral data for the early noninvasive detection of esophageal cancer and also try to apply similar approach to other cancer detection. From the perspective of molecular vibrational spectroscopy, this project attempts to reveal the principle about the configuration, conformation and composition variation of biomarker molecular during esophageal cancer occurrence and development process, which can help to elucidate the pathogenesis of cancer at the molecular level and provide experimental and theoretical basis for the early non-destructive screening of esophageal cancer.

食道癌是致死率很高的消化道恶性肿瘤，我国是食道癌高发区，急需发展早期无损筛查技术。尿液中携带有能够灵敏反映肿瘤存在及其发展状况的肿瘤标志物，但其浓度非常低，很难检测。表面增强拉曼光谱(SERS)技术的优势是检测灵敏度极高，特别适用于极低浓度的肿瘤标志物探测。而表面增强拉曼光活性（简称SEROA）能够更深层次反映普通拉曼光谱无法检测到的手性分子高级结构变化的信息。本项目在国际上首次专门对尿液中修饰核苷和蛋白类肿瘤标志物开展SERS和SEROA光谱检测分析，并结合分类与回归等多种统计方法开展食道癌无损筛查研究。项目所采用的检测方法能够排除其它因素干扰，极大增强与癌症密切相关的肿瘤标志物拉曼光谱信号，并可能将此方法推广应用于其它癌症检测研究。我们将从分子振动光谱的角度探讨肿瘤标志物分子在食道癌发生、发展过程中其构型、构象和构成比例等发生变化的规律，为食道癌早期无损检测提供实验和理论依据。

当今癌症已经成为威胁人类健康的头号敌人，全世界每年数以万计的病人死于癌症。由于癌症早期症状不明显，大多数癌症患者被发现时已是中、晚期，致使大部分癌症的致死率极高。因此，发展癌症早期无损筛查方法是当前生命科学研究领域核心课题。尿液中携带有能够灵敏反映肿瘤存在及其发展状况的肿瘤标志物，但其浓度非常低，很难检测。表面增强拉曼光谱(SERS)技术的优势是检测灵敏度极高，特别适用于极低浓度的肿瘤标志物探测。而表面增强拉曼光活性（简称SEROA）能够更深层次反映普通拉曼光谱无法检测到 的手性分子高级结构变化的信息。本项目在国际上首次专门对尿液中修饰核苷和蛋白类肿瘤标志物开展SERS和SEROA光谱检测分析，并结合分类与回归等多种统计方法开展食道癌无损筛查研究。项目所采用的检测方法能够排除其它因素干扰，极大增强与癌症密切相关的肿瘤标志物拉曼光谱信号，并可能将此方法推广应用于其它癌症检测研究。我们从分子振动光谱的角度探讨肿瘤标志物分子在食道癌发生、发展过程中各种成分发生变化的规律，为食道癌早期无损检测提供实验和理论依据。. 此外，在本项目执行过程中，我们课题组还创新性的提出利用特殊的金属羰基化合物在拉曼静默区具有拉曼光谱的特性，结合多种表面增强拉曼光谱和分子印迹技术，设计出三种基于SERS光谱技术的比率检测法对癌症患者体液中游离态肿瘤标志物包括CEA、EB病毒DNA等进行超灵敏定量检测。在本项目执行期内，项目负责人冯尚源作为第一作者或通讯作者共发表SCI二区以上论文13篇，其中SCI一区论文4篇，影响影子8以上论文3篇。同时申请发明专利6项，目前已经授权发明专利3项，本项目已经超额完成原先的预定目标。