MMP11mAb-SPIO探针用于探索下咽癌浸润与亚临床淋巴结转移规律的MRI分子影像研究

Submucous invasion and early lymph node metastasis are the main causes of poor prognosis of hypopharyngeal squamous cell carcinoma (HSCC). Conventional image technology cannot show the invasion boundary of primary HSCC, nor can show subclinical lymph node metastasis lesions with diameter less than 1 mm. Therefore, it’s difficult for conventional image technology to provide accurate guidance for the surgery and radiotherapy of HSCC. Accurate display of molecular boundaries of HSCC invasion, characteristics and distribution of subclinical lymph node metastasis by molecular imaging technology, as well as optimization of treatment regimen on this basis are the key to improve the diagnosis and treatment of HSCC. This project based on our previous study results of HSCC’s RNA-seq and select one significant differentially expressed gene MMP11 as molecular target. This gene is closely related to tumor invasion and lymph node metastasis. We will establish a molecular probe MMP11mAb-SPION, and then use MRI to identify invasion boundary of primary HSCC and subclinical lymph node metastasis. We will reveal the characteristics of invasion and metastasis of HSCC and explore their regularity, which will lay the foundation of optimizing HSCC’s surgery and radiotherapy and establish individualized treatment system for HSCC even carcinoma.

下咽癌粘膜下浸润与早期淋巴结转移是其预后不良的主要原因。目前的影像技术既不能准确显示下咽癌病灶的浸润边界，也不能显示直径小于1mm的亚临床淋巴结转移病灶，无法为下咽癌手术、放疗方案的制定提供精确的指导。采用分子影像技术，准确显示下咽癌浸润的分子边界、亚临床淋巴结转移病灶及其分布范围，在此基础上优化治疗方案，是提升下咽癌诊治水平的关键。本项目拟利用课题组前期对15例下咽癌手术切除标本进行基因测序和生物信息学分析的结果，选择在下咽癌病灶和病灶旁正常组织中呈显著差异表达且与肿瘤浸润与转移潜能密切相关的MMP11基因作为靶点，构建MMP11mAb-SPIO分子探针，使用MRI分子影像技术来研究下咽癌浸润的分子边界与亚临床淋巴结转移病灶的分子影像特征。揭示下咽癌浸润、转移的特点并探索其规律，为建立下咽癌个体化诊疗体系打下基础，进而提升肿瘤的个体化诊治水平。

本研究为解决下咽癌微浸润与早期淋巴结转移致其预后不良的问题，克服目前的影像学技术不能准确显示下咽癌病灶的微浸润边界及亚临床淋巴结转移病灶的缺点，采用分子影像学技术，准确显示下咽癌微浸润的分子边界、亚临床淋巴结转移病灶及其分布范围，以优化治疗方案。具体做法为：将在下咽癌组织中筛选出的显著差异表达且与肿瘤浸润与转移潜能密切相关的MMP11基因作为靶点，建立MMP11mAb-SPIO分子探针和裸鼠移植瘤模型，利用MRI分子影像学技术研究下咽癌微浸润的分子边界与亚临床淋巴结转移病灶的精准定量特征，并与病理学（包含免疫组化）检查结果对照，通过MRI图像预处理、病灶勾画、特征提取等步骤，初步构建了检测下咽癌微浸润分子边界的机器学习模型。本研究成果可能大幅提升下咽癌微浸润与亚临床转移病灶的检出水平，降低下咽癌手术和放疗后原位复发与颈淋巴结复发的机率，并为制定下咽癌个体化精准手术、放疗方案打下基础。