基于多模态分子影像特征的结直肠癌早期肝转移新分子标记物筛选及预测模型构建

Liver metastasis is the emphasis and challenge in the treatment of colorectal cancer. It is crucial to evaluate metastatic potential of cancer cells for early diagnosis. Multi-modality molecular imaging can reflect the metastasis-related changes in biological characteristics, and abnormal gene expression closely relate to liver metastases of colorectal cancer. The combination of multi-modality molecular imaging features and differential gene expression has high clinical application value in assessment of liver metastatic potential. Therefore, through the multi-stage and multi-spot detection of expression of metastasis-associated in colon cancer1 (MACC1) and its target gene SPON2 and related receptor LGR5 in the process of colorectal liver metastases.This project will assess their significances as candidate molecular markers for early liver metastases of colorectal cancer. This study will clarify the roles and mechanism of these new molecular markers in the promotion of metastasis through experiments in vitro cancer cells and in animal model for early liver metastasis in order to establish the correlation between new molecular markers and multi-modality imaging indicators. On this basis, early diagnosis and prognosis evaluation model for colorectal cancer liver metastasis integrating multi-modality imaging features with biological characteristics is built by means of Naive Bayes classifier, and the platform of computer aided diagnosis system of colorectal cancer liver metastasis is also established by network programming technology.The achievements of this research can provide effective means and tools for early diagnosis, prejudgement, prognosis assessment and the screening of new molecular markers of liver metastasis.

结直肠癌肝转移是结直肠癌治疗的重点和难点，评价转移潜能是早期诊断的关键。多模态分子影像能体现肝转移相关生物学特性变化，异常的基因表达与结直肠癌肝转移密切相关，结合多模态分子影像特征和基因差异表达对评价肝转移潜能具有较高的临床应用价值。为此，本项目在结直肠癌肝转移过程中多阶段、多位点检测结直肠癌转移相关基因1（MACC1）及其靶基因SPON2和相关受体LGR5的表达谱系，评估其作为结直肠癌早期肝转移候选分子标记物的重要性。在结直肠癌细胞和早期肝转移动物模型中，阐明这些新分子标记物的促转移作用机制，建立新分子标记物与多模态影像指标的关系。在此基础上，基于朴素贝叶斯分类器构建集多模态影像特征和生物学特性于一体的结直肠癌肝转移早期诊断评估预后模型，并利用网络编程技术构建结直肠癌肝转移的计算机辅助诊断系统平台。本课题的研究为结直肠癌肝转移早期诊断、预判、预后评估和新分子标记物筛选提供有效手段和平台。

结直肠癌肝转移是结直肠癌治疗的重点和难点，评价转移潜能是早期诊断的关键。多模态分子影像能体现肝转移相关生物学特性变化，异常的基因表达与结直肠癌肝转移密切相关，结合多模态分子影像特征和基因差异表达对评价肝转移潜能具有较高的临床应用价值。为此，本项目在结直肠癌肝转移过程中多阶段、多位点检测结直肠癌转移相关基因1（MACC1）及其靶基因SPON2和相关受体LGR5的表达谱系，评估其作为结直肠癌早期肝转移候选分子标记物的重要性。在结直肠癌细胞和早期肝转移动物模型中，阐明这些新分子标记物的促转移作用机制，建立新分子标记物与多模态影像指标的关系。.目前，本项目已基本完成了①早期肝转移相关生物学特性指标的选择和转移能力的评价，进行了结直肠癌早期肝转移影像检测手段的选择、多探针PET显像分析和多模态分子影像的融合。最终获得了能够进行体内、外转移生物学特性分析判别的多模态分子影像特征。②明确了 MACC1/SPON2/LGR5调控通路在结直肠癌肝转移病理机制中的重要性，并在体外肿瘤细胞系、结直肠癌肝转移动物模型中建立 MACC1/SPON2/LGR5调控通路的表达与肿瘤进展、转移的相关性。③本研究建立了高精度、高分辨率和高探测率的多模态分子影像成像方法，明确了能反映肝转移生物学特性和能评价转移能力的多探针分子影像显像规律，提供了研究肝转移发生分子机制、转移潜能评价、转移早期诊断、 转移预后预测的影像学新方法。④课题组首次建立了“LncRNA2Target v2.0综合数据库”，聚集了lncRNA对蛋白编码基因的靶向关联信息，这为基于朴素贝叶斯分类开发结直肠癌早期肝转移诊断评估和预后模型的深入研究积累了丰富的统计学经验和算法基础。

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