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中华肺部疾病杂志(电子版) ›› 2020, Vol. 13 ›› Issue (03) : 365 -370. doi: 10.3877/cma.j.issn.1674-6902.2020.03.015

药物与临床

厄洛替尼耐药的非小细胞肺癌细胞的差异表达mRNAs和lncRNAs分析
李树斌1, 于鸿2,(), 张耿月2   
  1. 1. 102600 北京,中国中医科学院广安门医院南区内一科
    2. 130012 长春,吉林省肿瘤医院 吉林省肿瘤防治研究所细胞生物研究室
  • 收稿日期:2019-12-23 出版日期:2020-06-25
  • 通信作者: 于鸿
  • 基金资助:
    吉林省卫生技术创新项目(2017J025)

Differential expression of mRNA and lncRNA in erlotinib-resistant non-small cell lung cancer cells

Shubin Li1, Hong Yu2,(), Gengyue Zhang2   

  1. 1. Department of Internal Medicine 1, South District, Guang′anmen Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 102600, China
    2. Department of Cell Biology, Institute of Cancer Prevention and Control, Jilin Provincial Cancer Hospital, Changchun 130012, China
  • Received:2019-12-23 Published:2020-06-25
  • Corresponding author: Hong Yu
引用本文:

李树斌, 于鸿, 张耿月. 厄洛替尼耐药的非小细胞肺癌细胞的差异表达mRNAs和lncRNAs分析[J/OL]. 中华肺部疾病杂志(电子版), 2020, 13(03): 365-370.

Shubin Li, Hong Yu, Gengyue Zhang. Differential expression of mRNA and lncRNA in erlotinib-resistant non-small cell lung cancer cells[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(03): 365-370.

目的

筛选并分析厄洛替尼耐药的非小细胞肺癌细胞的差异表达mRNAs和lncRNAs。

方法

在Gene Expression Omnibus(GEO)数据库中挑选数据集GSE80344,其数据来自厄洛替尼耐药的HCC827细胞和敏感细胞。通过GEO2R和探针匹配分析差异表达mRNAs和lncRNAs,筛选标准为|Fold change|>1.5,P value<0.01。通过Panther(http://www.pantherdb.org)、KEGG(http://www.kegg.jp/)、STRING(http://string-db.org)等数据库分析筛选得到的差异表达mRNAs和lncRNAs的可能的作用机制。通过TCGA(https://cancergenome.nih.gov/)数据库对筛选得到的关键mRNAs和lncRNAs进行生存分析验证。

结果

厄洛替尼耐药的HCC827细胞和敏感细胞相比,差异表达mRNAs共644个,差异表达lncRNAs共367个,其中128 mRNAs表达上调,516 mRNAs表达下调;137 lncRNAs表达上调,230 lncRNAs表达下调。这些mRNAs和lncRNAs主要涉及在PI3K-Akt、Ras、MAPK、ECM受体相互作用等与癌症密切相关的信号通路中发挥作用。基于数据库的分析验证结果与筛选结果一致。

结论

筛选分析得到的关健mRNAs和lncRNAs可为深入研究非小细胞肺癌EGFR-TKIs耐药机制的前期实验依据。

Objective

To identify the differential expression of mRNA and lncRNA in the erlotinib-resistant non-small cell lung cancer cells.

Methods

GSE80344 microarray datasets were selected from the Gene Expression Omnibus (GEO) database including the data from erlotinib-resistant HCC827 cells and sensitive cells. The aberrantly-expressed mRNAs and lncRNAs were analyzed by GEO2R and probe ID matching. The screening criteria were |Fold change|>1.5 and P value<0.01. The possible mechanisms of action of dysregulatory mRNAs and lncRNAs were investigated by Panther (http: //www.pantherdb.org), KEGG (http: //www.kegg.jp/), STRING (http: //string-db.org), and other databases. The candidate key mRNAs and lncRNAs obtained by screening were verified by survival analysis using the data from the TCGA database (https: //cancergenome.nih.gov/).

Results

Compared with the sensitive cells, there were 644 differentially-expressed mRNAs and 367 differentially-expressed lncRNAs in the erlotinib-resistant HCC827 cells, respectively, of which 128 mRNAs were up-regulated and 516 mRNAs were down-regulated. And 137 lncRNAs were up-regulated and 230 lncRNAs were down-regulated. These mRNAs and lncRNAs were mainly involved in the signaling pathways closely related to cancers, such as PI3K-Akt, Ras, MAPK, ECM receptor interactions, and so on. Database-based verification confirmed the screening results.

Conclusion

The screened out mRNAs and lncRNAs can provide theoretical and preliminary experimental bases for the further study on the mechanisms of EGFR-TKIs resistance of non-small cell lung cancer.

表1 厄洛替尼耐药的HCC827细胞的差异表达mRNAs(差异表达显著的前100 mRNAs,耐药细胞vs.敏感细胞)
图1 厄洛替尼耐药的HCC827细胞的差异表达mRNAs的GO分析结果图
图2 来自TCGA数据库的肺腺癌患者的总生存期分析
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