心理应激激素与肿瘤的发生发展密切相关，但其机制尚未阐明。我们前期工作结合TCGA数据库分析表明，心理应激可促使结直肠癌生长且NE水平显著增高，伴有TDG上调而NEIL1下调，后两者表达平衡失调致突变增加。TDG参与DNA主动去甲基化，NEIL1参与BER碱基修复通路，提示两者表达异常致使TDG的碱基切除和BER的碱基修复平衡被打破，使碱基修复错误率增加，干细胞发生突变的几率增大，从而使肠道干细胞向肿瘤干细胞转化，促进结直肠癌的发生。本研究拟采用体内体外实验分析NE的水平改变与TDG、NEIL1等的表达相关性及对结直肠癌的作用和调控机制；利用二代测序技术、标记物追踪、qRT-PCR等探究TDG、NEIL1对肠道干细胞突变影响及肠道干细胞瘤化机制，并分析其与结肠癌患者的临床相关性。研究意义旨在揭示NE诱导TDG/NEIL1的DNA修复失衡在肠道干细胞向肿瘤干细胞转化继而促结直肠癌发生的机制。

Psychological stress hormones and tumor occurrence and progression are closely related, but its mechanism has not yet elucidated. Our previous work and data from TCGA database showed that psychological stress could promote the growth of colorectal cancer and NE level was significantly increased, accompanied by TDG’supregulation and NEIL1’sdownregulation, the latter two express balance disorders to increase the mutation. TDG participates in DNA demethylation, NEIL1 participates in BER base repair pathway, suggesting that abnormal expression of both ends of the basement and the base repair balance of BER are broken, the base repair error rate increases, stem cell mutation Increased risk, so that the intestinal stem cells to tumor stem cells, and promote the occurrence of colorectal cancer. In this study, we used in vivo and in vitro experiments to analyze the relationship between the level of NE and the expression of TDG, NEIL1 and the mechanism and regulation of colorectal cancer. The effects of TDG and NEIL1 on the changes of intestinal stem cells and the mechanism of intestinal stem cell tumor were investigated by using two-generation sequencing technique, marker tracking and qRT-PCR to analyze its clinical relevance with colon cancer patients. The aim of the study was to reveal the mechanism of DNA repair imbalance of TDG / NEIL1 induced by NE in the transformation of intestinal stem cells into tumor stem cells and then promote the occurrence of colorectal cancer.