基于表面增强拉曼光谱技术的舌鳞状细胞癌手术切缘分子边界研究

Surgical resection remains the cornerstone of the treatment of oral squamous cell carcinoma(SSC), and intraoperative frozen section is used to ensure the negative surgical margins in order to achieve the complete resection of the tumor. The studies suggest that the molecular and metabolic alterations have occurred prior to the cellular morphological changes in the tumor cells, the frozen section can not ensure the total clean of the tumor cells, so it is very important that how to detect the molecular surgical margins in vivo quickly and accurately during the operation. In the previous our studies, we found the Raman spectroscopy could detect and discriminate the changes of molecular structures and component composition in the tongue SSC, premalignant tissues and normal mucosa. Meanwhile, it is found that the EGFR expression showed a stepped decreased in tongue SSC, pericarcinoma tissues and normal mucosa and could be used as the molecular margin biomarker. Based on the literatures and previous studies, we propose that Raman spectroscopy is applied to detect the surgical molecular margins of tongue SSC using EGFR as the biomarker. It is planned to produce the nano-probe which is able to combined with EGFR and labeled with Raman molecule in order to applied surface enhanced Raman spectroscopy to detect the surgical molecular margin of tongue SSC. Our research will provide the theoretical foundation and technique for the accurate detection in vivo of the surgical molecular margins and early diagnosis of tongue SSC in clinic, which can lower the incidence of the local recurrence and improve the prognosis and life qualities.

舌鳞状细胞癌治疗以手术为主，术中采用冰冻切片方法确保切缘阴性从而达到彻底切除肿瘤的目的。研究表明肿瘤细胞在发生形态学改变之前，其分子结构和生化代谢水平等已经发生改变，单纯依靠冰冻切片无法保证肿瘤细胞彻底清除，如何在术中原位、快速、准确地确定手术切缘的分子边界对舌癌治疗具有重要意义。我们前期研究发现拉曼光谱技术可以检测口腔黏膜癌变、癌前病变及正常组织中分子结构及物质组成的改变，并以此鉴别不同组织，同时发现在舌癌、癌旁及正常组织中EGFR表达呈梯度递减可以作为分子边界标志物。综上，我们提出以EGFR蛋白为标志物将拉曼光谱技术应用于舌鳞状细胞癌手术切缘分子边界检测的设想。本研究制备特异性结合EGFR蛋白的纳米探针，并标记拉曼活性分子用于拉曼光谱定位，应用表面增强拉曼光谱技术通过细胞、组织及动物学实验研究建立检测舌癌手术切缘分子边界的方法，为临床原位、快速界定舌癌肿瘤细胞的分子边界提供理论基础。

舌鳞状细胞癌的治疗以手术切除为主，术中采用病理冰冻切片方法确保手术切缘阴性从而达到彻底切除肿瘤的目的。研究表明肿瘤细胞在发生形态学改变之前，其分子结构和生化代谢水平等已经发生改变，单纯依靠冰冻切片无法保证肿瘤细胞彻底清除，如何在术中原位、快速、准确地确定手术切缘的分子边界对舌鳞状细胞癌的治疗具有重要意义。研究发现拉曼光谱技术可以检测口腔黏膜癌变、癌前病变及正常组织中分子结构及物质组成的改变，并以此鉴别不同组织，同时发现在舌鳞状细胞癌、癌旁及正常组织中EGFR表达呈梯度递减可以作为分子边界标志物。综上，我们提出以EGFR蛋白为标志物将拉曼光谱技术应用于舌鳞状细胞癌手术切缘分子边界检测的设想。本研究制备了EGFR抗体标记的纳米探针，通过细胞、动物等实验证明了该纳米探针良好的生物相容性及安全性，通过光谱检测证明了该探针局有良好的拉曼光谱活性。本研究将制备好纳米探针应用于细胞的增强拉曼检测，获得良好目标物质在细胞内的实时成像，通过动物及人体标本组织实验研究，建立了拉曼光谱快速、准确检测鳞状细胞癌组织的鉴别诊断模型，诊断准确率达80%以上。为临床原位、快速界定舌癌肿瘤细胞的分子边界及早期诊断提供理论基础，降低舌癌术后复发，提高患者的预后及生活质量。

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