Cited 83 times in
Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer
DC Field | Value | Language |
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dc.contributor.author | 김혜련 | - |
dc.contributor.author | 조병철 | - |
dc.contributor.author | 홍민희 | - |
dc.date.accessioned | 2020-12-01T17:22:22Z | - |
dc.date.available | 2020-12-01T17:22:22Z | - |
dc.date.issued | 2020-09 | - |
dc.identifier.issn | 1226-3613 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/180237 | - |
dc.description.abstract | Although approved programmed cell death protein (PD)-1 inhibitors show durable responses, clinical benefits to these agents are only seen in one-third of patients in most cancer types. Therefore, strategies for improving the response to PD-1 inhibitor for treating various cancers including non-small cell lung cancer (NSCLC) are urgently needed. Compared with genome and transcriptome, tumor DNA methylome in anti-PD-1 response was relatively unexplored. We compared the pre-treatment methylation status of cis-regulatory elements between responders and non-responders to treatment with nivolumab or pembrolizumab using the Infinium Methylation EPIC Array, which can profile ~850,000 CpG sites, including ~350,000 CpG sites located in enhancer regions. Then, we analyzed differentially methylated regions overlapping promoters (pDMRs) or enhancers (eDMRs) between responders and non-responders to PD-1 inhibitors. We identified 1007 pDMRs and 607 eDMRs associated with the anti-PD-1 response. We also identified 1109 and 1173 target genes putatively regulated by these pDMRs and eDMRs, respectively. We found that eDMRs contribute to the epigenetic regulation of the anti-PD-1 response more than pDMRs. Hypomethylated pDMRs of Cytohesin 1 Interacting Protein (CYTIP) and TNF superfamily member 8 (TNFSF8) were more predictive than programmed cell death protein ligand 1 (PD-L1) expression for anti-PD-1 response and progression-free survival (PFS) and overall survival (OS) in a validation cohort, suggesting their potential as predictive biomarkers for anti-PD-1 immunotherapy. The catalog of promoters and enhancers differentially methylated between responders and non-responders to PD-1 inhibitors presented herein will guide the development of biomarkers and therapeutic strategies for improving anti-PD-1 immunotherapy in NSCLC. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isPartOf | EXPERIMENTAL AND MOLECULAR MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Jae-Won Cho | - |
dc.contributor.googleauthor | Min Hee Hong | - |
dc.contributor.googleauthor | Sang-Jun Ha | - |
dc.contributor.googleauthor | Young-Joon Kim | - |
dc.contributor.googleauthor | Byoung Chul Cho | - |
dc.contributor.googleauthor | Insuk Lee | - |
dc.contributor.googleauthor | Hye Ryun Kim | - |
dc.identifier.doi | 10.1038/s12276-020-00493-8 | - |
dc.contributor.localId | A01166 | - |
dc.contributor.localId | A03822 | - |
dc.contributor.localId | A04393 | - |
dc.relation.journalcode | J00860 | - |
dc.identifier.eissn | 2092-6413 | - |
dc.identifier.pmid | 32879421 | - |
dc.identifier.url | https://www.nature.com/articles/s12276-020-00493-8 | - |
dc.contributor.alternativeName | Kim, Hye Ryun | - |
dc.contributor.affiliatedAuthor | 김혜련 | - |
dc.contributor.affiliatedAuthor | 조병철 | - |
dc.contributor.affiliatedAuthor | 홍민희 | - |
dc.citation.volume | 52 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 1550 | - |
dc.citation.endPage | 1563 | - |
dc.identifier.bibliographicCitation | EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.52(9) : 1550-1563, 2020-09 | - |
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