我们发现P75NGFR与结直肠癌的发生相关，可提高结直肠癌细胞化疗敏感性，但机制不详。初步研究发现P75NGFR可能通过增强S100A9介导的5-Fu诱导的凋亡和自噬进行调节。基于此假设，建立P75NGFR及S100A9高/低表达细胞株，生物学方法检测P75NGFR对结直肠癌化疗敏感性的影响；探讨P75NGFR调节化疗敏感性的方式及活化S100A9可能的分子机制；研究S100A9介导的Bcl-2/Beclin-1结合与平衡的分子机制；建立裸鼠成瘤模型，腹腔注射5-Fu，体内验证P75NGFR通过S100A9提高化疗药对肿瘤生长的抑制作用；组织芯片验证P75NGFR对术后化疗患者预后的预测作用。通过体内、外实验揭示P75NGFR激活S100A9介导Bcl-2/Beclin-1结合平衡调节结直肠癌化疗敏感性的机制。本研究对补充结直肠癌化疗耐药的分子机制，探寻新的化疗敏感性靶标有一定的临床意义。

P75NGFR is involved in tumorgenesis and progression of colorectal cancer(CRC), and increased the chemo-sensitivity of colorectal cancer cells to 5-Fu. However, the underlying mechanism remains unknown. Our preliminary experiments have demonstrated that P75NGFR may enhance the chemo-sensitivity via activating S100A9 mediating the autophagy and apoptosis induced by 5-Fu in colorectal cancer cells. Based on this hypothesis, the stable cells with over-expression/ knock-down of P75NGFR or S100A9 gens were established. In vitro, biological methods are used to investigate the effect of P75NGFR on chemo-sensitivity of colorectal cancer cells to 5-Fu, and to explore the mechanism of how P75NGFR enhancing the chemo-sensitivity. Furthermore, the signal pathway of how P75NGFR activating S100A9 gene and how S100A9 mediating the binding and balance of Bcl2/Beclin-1are also investigated. Then, in vivo, subcutaneous tumor models of colorectal cancer are established to verify whether P75NGFR increases the chemo-sensitivity of colorectal cancer cells to 5-Fu. Finally, based on the tissue microarray and following up data, we also assess whether P75NGFR or combined with S100A9 predict the outcome of colorectal cencer patients receiving standard 5-Fu based chemotherapy after radical surgery. On the basis of results mentioned above, we explore how P75NGFR enhances the chemo-sensitivity through activating S100A9 mediating the autophagy and apoptosis induced by 5-Fu in colorectal cancer cells. The clinical implication of this study is to provide some evidence to elucidate chemoresistence-related mechanism, and to seek a potentially novel target predicting chemo-sensitivity in colorectal cancer.