Evidence map›Paper›PMID 33976322›Full record

SynthesisScientific reports2021

Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy.

Jessica Hier, Olivia Vachon, Allison Bernstein, Iman Ibrahim, Alex Mlynarek, Michael Hier, Moulay A Alaoui-Jamali, Mariana Maschietto, Sabrina Daniela da Silva

Open access · goldAbstract readSystematic Review
In one paragraph

Synthesis in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

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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

9 authors at 3 institutions in 2 countries.

Jessica HierDepartment of Otolaryngology-Head and Neck Surgery, Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Olivia VachonDepartment of Otolaryngology-Head and Neck Surgery, Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Allison BernsteinDepartment of Otolaryngology-Head and Neck Surgery, Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Iman IbrahimDepartment of Otolaryngology-Head and Neck Surgery, Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Alex MlynarekDepartment of Otolaryngology-Head and Neck Surgery, Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Michael HierDepartment of Otolaryngology-Head and Neck Surgery, Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Moulay A Alaoui-JamaliSegal Cancer Centre of the Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Mariana MaschiettoDepartment of Structural and Functional Biology, Institute of Biology, Universidade Estadual de Campinas (UNICAMP) and Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
Sabrina Daniela da SilvaDepartment of Otolaryngology-Head and Neck Surgery, Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada. sabrina.wurzba@gmail.com.
Jewish General Hospital · CAMcGill University · CACentro Infantil Boldrini · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In addition to chronic infection with human papilloma virus (HPV) and exposure to environmental carcinogens, genetic and epigenetic factors act as major risk factors for head and neck cancer (HNC) development and progression. Here, we conducted a systematic review in order to assess whether DNA hypermethylated genes are predictive of high risk of developing HNC and/or impact on survival and outcomes in non-HPV/non-tobacco/non-alcohol associated HNC. We identified 85 studies covering 32,187 subjects where the relationship between DNA methylation, risk factors and survival outcomes were addressed. Changes in DNA hypermethylation were identified for 120 genes. Interactome analysis revealed enrichment in complex regulatory pathways that coordinate cell cycle progression (CCNA1, SFN, ATM, GADD45A, CDK2NA, TP53, RB1 and RASSF1). However, not all these genes showed significant statistical association with alcohol consumption, tobacco and/or HPV infection in the multivariate analysis. Genes with the most robust HNC risk association included TIMP3, DCC, DAPK, CDH1, CCNA1, MGMT, P16, MINT31, CD44, RARβ. From these candidates, we further validated CD44 at translational level in an independent cohort of 100 patients with tongue cancer followed-up beyond 10 years. CD44 expression was associated with high-risk of tumor recurrence and metastasis (P = 0.01) in HPV-cases. In summary, genes regulated by methylation play a modulatory function in HNC susceptibility and it represent a critical therapeutic target to manage patients with advanced disease.

Indexed as

DNA MethylationCarcinoma, Squamous CellGenetic Predisposition to DiseaseHead and Neck NeoplasmsHumansMolecular Targeted Therapy

Identifiers

PMID33976322
PMCPMC8113272
OpenAlexW3161597249

What OpenQuestion holds

Textmetadata
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.