微量元素分布对结直肠癌患者循环肿瘤细胞形成的影响及分子机制研究

结直肠癌是严重威胁我国居民健康的肿瘤之一，而微量元素(TEs) 改变在结直肠癌发生与发展中起重要作用并与其预后相关，循环肿瘤细胞（CTCs）出现是结直肠肿瘤转移的重要环节，是被FDA批准用于“液体活检”的指标，而结直肠癌患者TEs浓度及分布、对CTCs形成和转移的影响尚不清楚，阐明这种机制成为迫切需要解决的问题。我们前期的研究显示：结直肠癌患者全血中TEs改变明显，其中硒和锰差异显著（P<0.01），且硒和肿瘤的分期呈正相关。据此，本课题拟先查明结直肠癌患者全血中的TEs和CTCs的改变情况，尝试探讨其相关性；并进一步通过结直肠癌细胞株、临床样本及动物模型深入探讨TEs对CTCs从原发灶到转移灶的生物学特性的影响；生物信息学方法查找TEs影响的下游信号分子并分析其影响机制；校正TEs后逆转CTCs改变及抗癌效果的研究。本研究将为结直肠癌转移、预后和治疗等方面提供积极的理论基础。

Colorectal cancer (CRC) is one of the most common cause of death in the country. Trace elements (TEs) changes is significantly related to the development and prognosis of CRC. Circulating tumor cells (CTCs) formation is an important step of CRC metastasis, and also is the FDA approved liquid biopsy marker. The blood TEs concentration, distribution and effect on CTCs formation and CRC metastasis are unclear. And to clarify those issues are essential. Our previous studies showed that the blood TEs level, especially Se and Mn, was significantly changed in CRC patients(P<0.01). And the reduce of Se is positive to CRC TNM stages. According to those studies, we prepare to analyze the changes and relationship of TEs to CTCs, explore the effect of TEs changes to the biological characteristics of CTCs from primary tumor to metastasis by using cancer cell lines, human samples and mice models. Bioinformatics analysis will be used to find the downstream signals and the mechanism. TEs supplement or adjustment will be used for preventing CTCs formation and taking anticancer treatment. This study will provide positive theories for CRC metastasis, prognosis and treatment.