上皮膜蛋白-1作为胃肠道间质瘤耐药标志物的研究

Epithelial membrane protein-1 is a biomarker of Imatinib-resistant gastrointestinal stromal tumors

目的寻找胃肠道间质瘤（GIST）患者格列卫耐药的标记物，指导格列卫的临床用药。方法采用免疫组织化学方法比较格列卫规范治疗后，耐药的患者耐药前后上皮膜蛋白-1（EMP-1）蛋白的表达水平。将GIST882细胞种植于裸鼠皮下形成移植瘤，裸鼠持续口服伊马替尼3周后传代，直至移植瘤耐药。比较耐药移植瘤与敏感移植瘤中EMP-1基因和蛋白表达水平的差异。结果伊马替尼耐药后，患者及移植瘤肿瘤组织中EMP-1表达较耐药前显著增加，伊马替尼耐药移植瘤中EMP-1的RNA水平较敏感移植瘤增加约11倍。结论EMP-1可以作为GIST耐药的标志物。

Objective To find a biomarker of imatinib-resistant gastrointestinal stromal tumors （ GIST）, and further to explore a solution to Imatinib-resistance. Methods To Compare the expression of epithelial membrane protein-1 （EMP-1） between the Imatinib-sensitive GIST and the Imatinib-resistant GIST of the same patient by immunohistochemisty. A model of Imatinib-resistant nude mice xenograft was proposed by durative Imatinib treatment of the nude mice bearing subcutaneous GIST882 xenograft tumors. Then the expression of EMP-1 was compared in Imatinib-sensitive nude mice xenograft tumors and Imatinib-resistant xenograft tumors by immunohistochemisty and quantitative real-time polymerase chain reaction （qRT-PCR）. Results EMP-1 was overexpressed in Imatinib-resistant GIST patient and nude mice xeno- graft tumors. The mRNA level in Imatinib-resistant nude mice xenograft tumors was 11-fold higher than that in Imatinib-sensitive nude mice xenograft tumor.