Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment
文献类型：期刊论文
| 作者 | Niu, Xiaomin2; Zhou, Zhen2; Li, Ziming2; Ye, Xiangyun2; Yu, Yongfeng2; Liao, Meilin2; Chen, Zhiwei2; Lu, Shun2; Liu, Fatao3,4; Wang, Ting3,4 |
| 刊名 | CLINICAL CANCER RESEARCH
 |
| 出版日期 | 2017 |
| 卷号 | 23期号:17页码:5003-5014 |
| 关键词 | cell line gene expression incremental feature selection Monte Carlo feature selection support vector machine |
| ISSN号 | 1078-0432 |
| DOI | 10.1158/1078-0432.CCR-16-2688 |
| 文献子类 | Article |
| 英文摘要 | Purpose: The past decade has witnessed the rapid development of personalized targeted therapies in lung cancer. It is still unclear whetherepigeneticchangesare involved in the responseto tyrosine kinase inhibitor (TKI) treatment in epidermal growth factor receptor (EGFR)-mutated lung cancer. Experimental Design: Methyl-sensitive cut counting sequencing (MSCC) was applied to investigate the methylation changes in paired tissues before and after erlotinib treatment for 42 days with partial response (PR) from stage IIIa (N2) lung adenocarcinoma patients (N = 2) with EGFR 19 deletion. The Sequenom EpiTYPER assay was used to validate the changed methylated candidate genes. Up-or downregulation of the candidate gene was performed to elucidate the potential mechanism in the regulation of erlotinib treatment response. Results: Sixty aberrant methylated genes were screened using MSCC sequencing. Two aberrant methylated genes, CBFA2T3 and GABBR2, were clearly validated. A same differential methylated region (DMR) between exon 2 and exon 3 of GABBR2 gene was confirmed consistently in both patients. GABBR2 was significantly downregulated in EGFR 19 deletion cells, HCC4006 and HCC827, but remained conserved in EGFR wild-type A549 cells after erlotinib treatment. Upregulation of GABBR2 expression significantly rescued erlotinib-induced apoptosis in HCC827 cells. GABBR2 was significantly downregulated, along with the reduction of S6, p-p70 S6, and p-ERK1/2, demonstrating that GABBR2 may play an important role in EGFR signaling through the ERK1/2 pathway. Conclusions: We demonstrated that GABBR2 gene might be a novel potential epigenetic treatment target with induction erlotinib treatment for stage IIIa (N2) EGFR 19 deletion lung adenocarcinoma. (C) 2017 AACR. |
| 学科主题 | Oncology |
| WOS关键词 | LARGE GENE LISTS ; CANCER CELLS ; EXPRESSION ; PATHWAY ; HYPERMETHYLATION ; ACTIVATION ; GEFITINIB ; PROGNOSIS ; CETUXIMAB ; MUTATION |
| 语种 | 英语 |
| WOS记录号 | WOS:000409037300007 |
| 出版者 | AMER ASSOC CANCER RESEARCH |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1058]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China; 2.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Shanghai Lung Canc Ctr, 241 Huaihai West Rd, Shanghai 200030, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gen Surg, Shanghai, Peoples R China; 4.Shanghai Jiao Tong Univ, Inst Biliary Tract Dis, Sch Med, Shanghai, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China; 6.Shanghai Jiao Tong Univ, Key Lab Genet Dev & Neuropsychiat Disorders, BioX Inst, Minist Educ, Shanghai, Peoples R China; 7.Fudan Univ, Dept Biochem & Mol Biol, Key Lab Mol Med, Minist Educ,Shanghai Med Coll, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Niu, Xiaomin,Zhou, Zhen,Li, Ziming,et al. Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment[J]. CLINICAL CANCER RESEARCH,2017,23(17):5003-5014. |
| APA | Niu, Xiaomin.,Zhou, Zhen.,Li, Ziming.,Ye, Xiangyun.,Yu, Yongfeng.,...&,.(2017).Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment.CLINICAL CANCER RESEARCH,23(17),5003-5014. |
| MLA | Niu, Xiaomin,et al."Genome-wide DNA Methylation Analysis Reveals GABBR2 as a Novel Epigenetic Target for EGFR 19 Deletion Lung Adenocarcinoma with Induction Erlotinib Treatment".CLINICAL CANCER RESEARCH 23.17(2017):5003-5014. |
入库方式： OAI收割
来源：上海营养与健康研究所
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