Yu Yongkang, Luo Yaohui, Zheng Yifeng, Zheng Xiushan, Li Wei, Yang Lie, Jiang Jianqing
Department of Thoracic Surgery, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu, China.
J Cancer Res Ther. 2016 Jan-Mar;12(1):121-5. doi: 10.4103/0973-1482.151425.
Here we aimed to explore the possible mechanism and potential regulatory relationships in which the non.small.cell lung cancer. (NSCLC)-resisted epidermal growth factor receptor. (EGFR) tyrosine kinase inhibitor erlotinib.
GSE38310, the gene expression profiles of NSCLC cell lines treated with dimethylsulfoxide or erlotinib, including HCC827, ER3, and T15-2, were downloaded from Gene Expression Omnibus database and preprocessed by normalization. Basing on the regulatory relationships of transcriptional factors obtained from University of California Santa Cruz. (UCSC) database, the differentially expressed genes. (DEGs) were screened using limma package in R with. |logFC| >1 and P < 0.05, and regulatory networks of these DEGs were built with supervised inference of regulatory networks (SIRENE). Subsequently, differentially regulatory networks were compared basing on Limit Fold Change. (LFC) method.
Totally 24,380 genes were obtained, 1,531 DEGs were identified in HCC827 cell lines, 37 DEGs in ER3 cell lines, 156 DEGs in T15-2 cell lines. After removing the redundancy genes, 1,575 differentially expressed genes were got at last. Basing on three regulatory networks of HCC827 cell lines, ER3 cell lines and T15-2 cell lies, sex-determining region Y (SRY).related high mobility group-box gene 9. (SOX9) and Suppressor of cytokine signaling 3 (STAT3) were identified by comparing with HCC827 and ER3 networks. And suppressor of cytokine signaling 5 B (STAT5B), early growth response-1 (EGR1) and STAT6 were obtained in comparison of HCC827 and T15-2 networks.
The regulatory edges with remarkable changes between HCC827 and ER3, HCC827 and T15.2 included some transcription factors and genes. (e. g., STAT3 and SOX9). STAT3, SOX9, STAT5B, EGR1, and STAT6 might affect the resistance of NSCLC to erlotinib.
本研究旨在探索非小细胞肺癌（NSCLC）对表皮生长因子受体（EGFR）酪氨酸激酶抑制剂厄洛替尼耐药的可能机制及潜在调控关系。
从基因表达综合数据库下载用二甲基亚砜或厄洛替尼处理的NSCLC细胞系（包括HCC827、ER3和T15-2）的基因表达谱GSE38310，并进行标准化预处理。基于从加利福尼亚大学圣克鲁兹分校（UCSC）数据库获得的转录因子调控关系，使用R语言中的limma软件包筛选差异表达基因（DEG），|logFC|>1且P<0.05，并通过监管网络的监督推理（SIRENE）构建这些DEG的调控网络。随后，基于极限倍数变化（LFC）方法比较差异调控网络。
共获得24380个基因，在HCC827细胞系中鉴定出1531个DEG，在ER3细胞系中鉴定出37个DEG，在T15-2细胞系中鉴定出156个DEG。去除冗余基因后，最终得到1575个差异表达基因。基于HCC827细胞系、ER3细胞系和T15-2细胞系的三个调控网络，通过与HCC827和ER3网络比较，鉴定出性别决定区Y（SRY）相关高迁移率族盒基因9（SOX9）和细胞因子信号转导抑制因子3（STAT3）。通过比较HCC827和T15-2网络，获得了细胞因子信号转导抑制因子5B（STAT5B）、早期生长反应因子-1（EGR1）和STAT6。
HCC827与ER3、HCC827与T15-2之间具有显著变化的调控边包括一些转录因子和基因（如STAT3和SOX9）。STAT3、SOX9、STAT5B、EGR1和STAT6可能影响NSCLC对厄洛替尼的耐药性。
