[1]苗留飞,杨 阳,余柏增,等.三代EGFR-TKI奥希替尼(AZD9291)耐药细胞系建立及耐药标志预测分析[J].现代检验医学杂志,2019,34(05):28-31.[doi:10.3969/j.issn.1671-7414.2019.05.008]
　MIAO Liu-fei,YANG Yang,YU Bai-zeng,et al.Establishment of the Third Generation of EGFR-TKI Resistant CellLine and Resistance Gene Signature[J].Journal of Modern Laboratory Medicine,2019,34(05):28-31.[doi:10.3969/j.issn.1671-7414.2019.05.008]
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三代EGFR-TKI奥希替尼(AZD9291)耐药细胞系建立及耐药标志预测分析()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第34卷
期数:
2019年05期
页码:
28-31
栏目:
论著
出版日期:
2019-10-29

文章信息/Info

Title:
Establishment of the Third Generation of EGFR-TKI Resistant CellLine and Resistance Gene Signature
文章编号:
1671-7414(2019)05-028-04
作者:
苗留飞; 杨 阳; 余柏增; 张家勋; 李晓军
(南京大学医学院附属金陵医院/东部战区总医院中心实验科,南京 210002)
Author(s):
MIAO Liu-fei; YANG Yang; YU Bai-zeng; ZHANG Jia-xun; LI Xiao-jun
(Department of Clinical Laboratory,Jinling Hospital AffiliatedNanjing University Medical College/General Hospital of Eastern Theater Command,Nanjing 210002,China)
关键词:
表皮生长因子受体;  酪氨酸激酶抑制剂;  非小细胞肺癌;  奥希替尼(AZD9291);  耐药标志
分类号:
R734.2; R730.43
DOI:
10.3969/j.issn.1671-7414.2019.05.008
文献标志码:
A
摘要:
目的 建立三代表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)奥希替尼耐药细胞系(PC9-OR)并分析其耐药标志。方法 浓度梯度递增构建奥希替尼耐药PC9细胞系(PC9-OR)。利用生物信息学分析AZD9291耐药细胞株表达谱芯片和测序数据筛选出耐药细胞高表达基因; 荧光定量PCR验证表达; Logistics构建回归诊断模型并用ROC曲线验证其诊断效能。结果 成功构建PC9-OR耐药细胞株,对3组独立PC9-OR细胞表达谱数据生物信息分析,发现19个基因表达在至少两个数据集中表达上调,3个基因在3个耐药细胞数据集表达均上调。荧光定量PCR检测PC9-OR细胞耐药相关基因有11个表达上调。Logistics回归显示5个基因诊断效能较好,ROC联合诊断模型显示曲线下面积0.985。结论 构建了三代EGFR-TKI奥希替尼耐药细胞系PC9-OR,发现一组基因可以作为EGFR-TKI耐药的标志,可能为临床及时发现EGFR-TKI耐药提供依据。
Abstract:
Objective To identify molecular signature of third generation EGFR-TKI(AZD9291)acquired resistance.Methods AZD9291 drug-resistant PC9 cell line(PC9-OR)was established by concentration gradient increment method.AZD9291 resistance-related genes were obtained by integrated analysis of drug-resistant cell lines expression profiles fromGEO database.The expressions of all genes were verified by fluorescence quantitative PCR.The diagnostic efficacy of resistant signature was verified by logistic regression and ROC curve in an independent GEO profile.ResultsPC9-OR cell line was successfully constructed.It was found that 19genes were up-regulated in at least two independent datasets and 3 genes were up-regulated in three drug-resistant cell datasets.Eleven of them was confirmed in PC9-OR cells by fluorescence quantitative PCR.The signature of drug-resistant cells was obtained by using logistic regression.The area under ROC curvewas 0.982 2 in GSE34228.Conclusion Constructed a cell line which was resistant to the third generation EGFR-TKI.Based on cell lineandlarge scale datasets,definite a resistance signature for EGFR-TKI,which mayprovide a basis for detection of EGFR-TKI resistance in clinical use.

参考文献/References:

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备注/Memo

备注/Memo:
基金项目:国家临床重点专科建设项目(2014ZDZK003-1); 江苏省博士后基金(2018K280C)。 作者简介:苗留飞(1994-),男,硕士,主要从事肺癌靶向药耐药标志的研究,E-mail:1939187763@qq.com。 通讯作者:李晓军,女,主任技师,博士后导师,主要从事肿瘤实验诊断研究,E-mail:xiaojunli62@126.com。
更新日期/Last Update: 2019-10-20