表皮生长因子受体在肺癌相关静脉血栓栓塞症发生中的作用

Venous thrombosis (VTE) is a common complication and cause of death in lung cancer. Epidermal growth factor receptor (EGFR) is a common driving gene and therapeutic target for non-small cell lung cancer. Oncogene can be involved in the regulation of coagulation-related tissue factor expression and affect the occurrence of VTE. Our prospective cohort study found that EGFR mutations reduced the risk of VTE in patients with NSCLC. However, how does EGFR gene affect VTE in patients with NSCLC? There are no reports yet. In this study, we plan to follow up clinical cases of lung cancer, culture EGFR mutant and wild type cell lines, and establish xenograft tumor model and tumor with VTE animal model. These experiments aim to determine the exact relationship between EGFR mutations and EGFR tyrosine kinase inhibitors and VTE, to determine the difference in coagulation mechanism between EGFR mutant and wild-type tumors, and to explore the relationship between EGFR mutations and tumor tissue secreting tissue factor and its regulatory mechanism. The completion of this project will help to further understand the molecular mechanism of VTE associated with lung cancer,and to explore its predicting biomarkers which provide new ideas for its prevention and treatment.

静脉血栓栓塞症（VTE）是肺癌常见的并发症和死亡原因。表皮生长因子受体( EGFR)基因是非小细胞肺癌常见的驱动基因和治疗靶点。癌基因可参与调控凝血相关组织因子的表达而影响VTE的发生。我们通过前瞻性队列研究发现，非小细胞肺癌EGFR突变患者VTE的发生风险降低，然而EGFR基因是如何影响非小细胞肺癌患者VTE发生的研究尚未见报道。本研究拟通过随访临床非小细胞肺癌病例、培养及干预EGFR突变型和EGFR野生型细胞系、建立异种移植肿瘤模型及肿瘤合并VTE动物模型等实验，明确EGFR突变和应用EGFR酪氨酸激酶抑制剂与VTE发生的确切关系，确定EGFR突变肿瘤与EGFR野生型肿瘤发生VTE的凝血机制的差异，及探讨EGFR突变与肿瘤细胞分泌组织因子的关系及调控机制。本项目的完成将有助于深入认识肺癌相关VTE发生的分子机制，进一步探索预测肿瘤相关VTE发生的生物标志物，对其防治提供新思路。

静脉血栓栓塞症（VTE）是肺癌常见的并发症和死亡原因。癌基因可参与调控凝血相关组织因子的表达而影响VTE的发生。本研究我们通过前瞻性队列研究发现，非小细胞肺癌EGFR突变患者VTE的发生风险降低，且EGFR突变合并VTE患者早期死亡风险较野生型VTE患者低，ALK重排患者VTE发生风险明显升高。本研究着眼于EGFR突变、ALK重排引起血栓的机制，发现ALK融合蛋白可通过调控肿瘤细胞分泌组织因子，调控血液高凝。本研究结果为肿瘤相关VTE的防治提供了了新思路。