Evidence map›Paper›PMID 31628024›Full record

ArticleEBioMedicine2019

DNA methylation of indoleamine 2,3-dioxygenase 1 (IDO1) in head and neck squamous cell carcinomas correlates with IDO1 expression, HPV status, patients' survival, immune cell infiltrates, mutational load, and interferon γ signature.

Verena Sailer, Ulrike Sailer, Emma Grace Bawden, Romina Zarbl, Constanze Wiek, Timo J Vogt, Joern Dietrich, Sophia Loick, Ingela Grünwald, Marieta Toma and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. The immunotherapeutic role of indoleamine 2,3-dioxygenase in head and neck squamous cell carcinoma: A systematic review.Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery · 2021
    Pooled it
  2. Review
  3. Immune Checkpoint Inhibitors in Clear Cell Renal Cell Carcinoma (ccRCC).International journal of molecular sciences · 2025
    Review
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  11. Proposed Pathway Linking Respiratory Infections with Depression.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2022
    Review
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  19. Review
  20. The landscape ofEpigenetics · 2020
    Article
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

17 authors at 5 institutions in 2 countries.

Verena SailerPathology of the University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Ulrike SailerDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Street 25, 53105 Bonn, Germany.
Emma Grace BawdenDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Romina ZarblDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Street 25, 53105 Bonn, Germany.
Constanze WiekDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Düsseldorf, Düsseldorf, Germany.
Timo J VogtDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Street 25, 53105 Bonn, Germany.
Joern DietrichDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Street 25, 53105 Bonn, Germany.
Sophia LoickDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Street 25, 53105 Bonn, Germany.
Ingela GrünwaldDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Street 25, 53105 Bonn, Germany.
Marieta TomaInstitute of Pathology, University Hospital Bonn, Bonn, Germany.
Carsten GolletzInstitute of Pathology, University Hospital Bonn, Bonn, Germany.
Andreas GerstnerDepartment of Otolaryngology, Head and Neck Surgery, Municipal Hospital Braunschweig, Braunschweig, Germany.
Glen KristiansenInstitute of Pathology, University Hospital Bonn, Bonn, Germany.
Friedrich BootzDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Street 25, 53105 Bonn, Germany.
Kathrin ScheckenbachDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Düsseldorf, Düsseldorf, Germany.
Jennifer LandsbergDepartment of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany.
Dimo DietrichDepartment of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Street 25, 53105 Bonn, Germany. Electronic address: dimo.dietrich@gmail.com.
University Hospital Bonn · DEDüsseldorf University Hospital · DEKlinikum Braunschweig · DEThe University of Melbourne · AUUniversity Hospital Schleswig-Holstein · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe immune checkpoint, indoleamine 2,3-dioxygenase 1, is under investigation as target of novel immunotherapies for cancers, including head and neck squamous cell carcinomas (HNSCC). The aim of our study was to analyze DNA methylation of the encoding gene (IDO1) in HNSCC.

methodsMethylation of three CpG sites within the promoter, promoter flank, and gene body was investigated and correlated with mRNA expression, immune cell infiltration, mutational burden, human papillomavirus (HPV)-status, and overall survival in a cohort of N = 528 HNSCC patients obtained from The Cancer Genome Atlas. In addition, IDO1 immunohistochemistry and DNA methylation analysis was performed in an independent cohort of N = 138 HNSCC samples.

findingsSignificant inverse correlations of IDO1 methylation and IDO1 mRNA expression were found in the promoter and promoter flank region (Spearman's ρ = -0.163 and ρ = -0.377, respectively) while a positive correlation was present in the gene body (ρ = 0.502; all P < 0.001). IDO1 DNA methylation significantly correlated with IDO1 protein expressing immune cells as well as tumor cells. IDO1 promoter flank hypermethylation was significantly associated with poor overall survival (P < 0.001). In addition, we discovered significant correlations between IDO1 methylation and expression with RNA signatures of immune cell infiltrates and with HPV-status, mutational load (methylation only), and interferon γ signature.

interpretationOur results suggest IDO1 expression levels are epigenetically regulated by DNA methylation. This study provides rationale to test IDO1 methylation as potential biomarker for prediction of response to IDO1 immune checkpoint inhibitors in HNSCC.

Indexed as

DNA MethylationPapillomaviridaeBiomarkers, TumorCell Line, TumorCluster AnalysisCpG IslandsCytokinesFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryIndoleamine-Pyrrole 2,3,-DioxygenaseKaplan-Meier EstimateMalePapillomavirus InfectionsRNA, MessengerBiomarkers, TumorCytokinesIDO1 protein, humanIndoleamine-Pyrrole 2,3,-DioxygenaseRNA, MessengerDNA methylationHead and neck squamous cell carcinomaHPVIDO1, BiomarkerImmunotherapyIndoleamine 2,3-dioxygenase 1PredictionPrognosis

Identifiers

PMID31628024
PMCPMC6838413
OpenAlexW2981030158

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.