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

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。

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

ObjectiveTo identify the differential expression of mRNA and lncRNA in the erlotinib-resistant non-small cell lung cancer cells. MethodsGSE80344 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/). ResultsCompared 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. ConclusionThe 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.