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| DOI | 10.3390/biom11071042 |
| Computational Probing the Methylation Sites Related to EGFR Inhibitor-Responsive Genes | |
| Yuan, Rui; Chen, Shilong; Wang, Yongcui | |
| 通讯作者 | Wang, YC (通讯作者)，Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Plateau Biol Adaptat & Evolut, Xining 810008, Peoples R China. ; Wang, YC (通讯作者)，Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Crop Mol Breeding, Xining 810008, Peoples R China. |
| 发表日期 | 2021 |
| EISSN | 2218-273X |
| 卷号 | 11期号:7 |
| 英文摘要 | The emergence of drug resistance is one of the main obstacles to the treatment of lung cancer patients with EGFR inhibitors. Here, to further understand the mechanism of EGFR inhibitors in lung cancer and offer novel therapeutic targets for anti-EGFR-inhibitor resistance via the deep mining of pharmacogenomics data, we associated DNA methylation with drug sensitivities for uncovering the methylation sites related to EGFR inhibitor sensitivity genes. Specifically, we first introduced a grouped regularized regression model (Group Least Absolute Shrinkage and Selection Operator, group lasso) to detect the genes that were closely related to EGFR inhibitor effectiveness. Then, we applied the classical regression model (lasso) to identify the methylation sites associated with the above drug sensitivity genes. The new model was validated on the well-known cancer genomics resource: CTRP. GeneHancer and Encyclopedia of DNA Elements (ENCODE) database searches indicated that the predicted methylation sites related to EGFR inhibitor sensitivity genes were related to regulatory elements. Moreover, the correlation analysis on sensitivity genes and predicted methylation sites suggested that the methylation sites located in the promoter region were more correlated with the expression of EGFR inhibitor sensitivity genes than those located in the enhancer region and the TFBS. Meanwhile, we performed differential expression analysis of genes and predicted methylation sites and found that changes in the methylation level of some sites may affect the expression of the corresponding EGFR inhibitor-responsive genes. Therefore, we supposed that the effectiveness of EGFR inhibitors in lung cancer may be improved by methylation modification in their sensitivity genes. |
| 关键词 | GROWTH-FACTOR RECEPTORCELL LUNG-CANCERDNA METHYLATIONACQUIRED-RESISTANCEMUTATIONSSENSITIVITYREGRESSIONERLOTINIBSELECTIONPROMOTER |
| 英文关键词 | DNA methylation; group lasso; CTRP and CCLE; lung cancer; EGFR inhibitors effectiveness related methylation sites |
| 语种 | 英语 |
| WOS研究方向 | Biochemistry & Molecular Biology |
| WOS类目 | Biochemistry & Molecular Biology |
| WOS记录号 | WOS:000676358400001 |
| 来源期刊 | BIOMOLECULES
 |
| 来源机构 | 中国科学院西北生态环境资源研究院 |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/253627 |
| 作者单位 | [Yuan, Rui; Chen, Shilong; Wang, Yongcui] Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Plateau Biol Adaptat & Evolut, Xining 810008, Peoples R China; [Yuan, Rui] Univ Chinese Acad Sci, Beijing 100049, Peoples R China; [Chen, Shilong] Chinese Acad Sci, Inst Sanjiangyuan Natl Pk, Xining 810008, Peoples R China; [Wang, Yongcui] Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Crop Mol Breeding, Xining 810008, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yuan, Rui,Chen, Shilong,Wang, Yongcui. Computational Probing the Methylation Sites Related to EGFR Inhibitor-Responsive Genes[J]. 中国科学院西北生态环境资源研究院,2021,11(7). |
| APA | Yuan, Rui,Chen, Shilong,&Wang, Yongcui.(2021).Computational Probing the Methylation Sites Related to EGFR Inhibitor-Responsive Genes.BIOMOLECULES,11(7). |
| MLA | Yuan, Rui,et al."Computational Probing the Methylation Sites Related to EGFR Inhibitor-Responsive Genes".BIOMOLECULES 11.7(2021). |
| 条目包含的文件 | 条目无相关文件。 | |||||
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