Evidence map›Paper›PMID 32879421›Full record

ArticleExperimental & molecular medicine2020

Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer.

Jae-Won Cho, Min Hee Hong, Sang-Jun Ha, Young-Joon Kim, Byoung Chul Cho, Insuk Lee, Hye Ryun Kim

Open access · goldAbstract read
In one paragraph

Article in Experimental & molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 1 pooled it
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

174 citing papers in PubMed, 1 synthesis or guideline pooled it, 279 citations in OpenAlex.

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114 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Jae-Won ChoDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Korea.
Min Hee HongDivision of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.ORCID http://orcid.org/0000-0003-3490-2195
Sang-Jun HaDepartment of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, 03722, Korea.ORCID http://orcid.org/0000-0002-1192-6031
Young-Joon KimDepartment of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, 03722, Korea.
Byoung Chul ChoDivision of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Insuk LeeDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Korea. insuklee@yonsei.ac.kr.ORCID http://orcid.org/0000-0003-3146-6180
Hye Ryun KimDivision of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea. nobelg@yuhs.ac.
Yonsei University · KR

Funding

National Research Foundation of Korea (NRF) 2016M3C9A4922809National Research Foundation of Korea (NRF) 2017M3A9E8029717National Research Foundation of Korea (NRF) 2017M3A9E9072669National Research Foundation of Korea (NRF) 2018M3C9A5064709National Research Foundation of Korea (NRF) 2018R1A5A2025079Yonsei University | Yonsei University College of Dentistry (YUCD) 6-2018-0072
6 · The paper itself

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.

Indexed as

Biomarkers, TumorDNA MethylationEnhancer Elements, GeneticGene Expression Regulation, NeoplasticPromoter Regions, GeneticAdultAgedAged, 80 and overCarcinoma, Non-Small-Cell LungFemaleHumansImmune Checkpoint InhibitorsImmune Checkpoint ProteinsImmunomodulationLung NeoplasmsMaleBiomarkers, TumorImmune Checkpoint InhibitorsImmune Checkpoint Proteins

Identifiers

PMID32879421
PMCPMC8080767
OpenAlexW3082682051

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.