EGFR外显子19缺失突变促恶性甲状腺肿瘤侵袭迁移作用的研究

The Role of EGFR Exon 19 Deletion Mutation in Promoting Invasion and Migration of Malignant Thyroid Tumors

目的研究表皮生长因子受体(EGFR)外显子19缺失突变(EGFR exon 19 deletion)在恶性甲状腺肿瘤中促侵袭转移的作用。方法划痕和Transwell实验检测细胞的迁移和侵袭能力;转录组测序分析(RNA-seq)检测HTFEC-ex19 del细胞株中调控肿瘤分子生物学的相关信号通路。结果分析发现4%(2/50)的甲状腺癌患者的基因组测序中具有EGFR突变。功能分析结果显示,EGFR外显子19缺失突变会使细胞具有迁移侵袭行为。RNA-seq分析结果显示,EGFR外显子19缺失突变后致癌基因KRAS通路、p53通路、EGFR下游相关信号通路PI3K-AKT、上皮间质转化(EMT)通路等显著富集。结论EGFR外显子19缺失突变可使细胞更具侵袭性,激活癌症相关通路,其中包括PI3K-AKT信号通路、EMT等通路。EGFR外显子19缺失突变可成为临床治疗甲状腺癌一个重要参考指标。

Objective To investigate the effect of epidermal growth factor receptor(EGFR)exon 19 deletion mutation on promoting invasion and metastasis of malignant thyroid tumor.Methods The invasiveness and migration capability was examined by wound-healing and Transwell.Related signaling pathways regulating tumor molecular biology in HTFEC-Ex19 del cell lines were observed by RNA-seq analysis.Results In this study,four percent(2/50)with EGFR mutation was found in thyroid cancer patients by genome sequencing.Functional analysis showed that EGFR exon 19 deletion mutation had migration and invasion behavior.Data of RNA-seq uncovered EGFR exon 19 deletion affects the oncogene KRAS pathway,p53 signal pathway,PI3K-AKT signal pathway downstream of EGFR and epithelial-mesenchymal transformation pathway.Conclusion EGFR exon 19 deletion mutation can make cells more aggressive and activate cancer-related pathways,including PI3K-AKT signaling pathway,EMT,etc.EGFR exon 19 deletion mutation may be an important reference index for clinical treatment of thyroid cancer.