PC4在非小细胞肺癌淋巴转移中的作用与机制研究

Non-small cell lung cancer is a common primary malignant tumor of the respiratory system, and it is of great significance to identify new specific and effective molecular targets for non-small cell lung cancer targeted therapy. Our previous work has demonstrated that transcriptional positive cofactor 4 (PC4) is related to stem cell proliferation regulation and malignant transformation process. Further studies have shown that the expression level of PC4 has a certain correlation with the progression and metastasis of non-small cell lung cancer, especially in those tumor tissues with lymph node metastasis PC4 expression is significantly increased. On the basis of above work, we put forward the hypothesis that PC4 may act as a gene related to lymphatic metastasis of non-small cell lung cancer. Firstly, we plan to further observe PC4 expression differences in different clinical stages of non-small cell lung cancer tissues, and clear the correlation between PC4 expression and lymphatic metastasis, as well as prognostic markers of non-small cell lung cancer. Secondly, we propose to reveal the influence of PC4 on lymphatic metastasis of non-small cell lung cancer by regulating PC4 expression in non-small cell lung cancer cells with different metastatic potential. Thirdly, we aim to clarify the role and mechanism of PC4 in lymphatic metastasis of non-small cell lung cancer by exploring the relationship between PC4 and VEGF-C/D-VEGFR-3 signaling pathways in non-small cell lung cancer.

非小细胞肺癌是呼吸系统常见的原发恶性肿瘤，寻找新的特异有效的分子靶标对于非小细胞肺癌靶向治疗具有重要意义。本项目前期工作中发现，转录辅助因子PC4（Transcriptional positive cofactor 4）与干细胞增殖调控和恶性转化过程相关，进一步研究发现，其表达水平与非小细胞肺癌进展及转移情况具有一定相关性，特别是发生淋巴结转移的肿瘤组织中PC4表达水平显著升高。在此基础上，本项目提出PC4可能作为非小细胞肺癌淋巴转移相关基因的假设，拟进一步观察不同临床分期非小细胞肺癌组织中PC4的表达差异，明确PC4与非小细胞肺癌淋巴转移及预后相关标志物的相关性；通过调控PC4在不同转移潜能非小细胞肺癌细胞中的表达，明确PC4对非小细胞肺癌淋巴转移的影响；进一步探讨PC4与非小细胞肺癌淋巴转移VEGF-C/D-VEGFR-3信号通路的关系，明确PC4在非小细胞肺癌淋巴转移中的作用及机制。