Evidence map›Paper›PMID 24223768›Full record

ArticlePloS one2013

Preferential activation of the hedgehog pathway by epigenetic modulations in HPV negative HNSCC identified with meta-pathway analysis.

Elana J Fertig, Ana Markovic, Ludmila V Danilova, Daria A Gaykalova, Leslie Cope, Christine H Chung, Michael F Ochs, Joseph A Califano

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

25 citing papers in PubMed, 41 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

8 authors at 4 institutions in 1 country.

Elana J FertigDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, United States of America.
Ana Markovic
Ludmila V Danilova
Daria A Gaykalova
Leslie Cope
Christine H Chung
Michael F Ochs
Joseph A Califano
Johns Hopkins University · USGreater Baltimore Medical Center · USSidney Kimmel Comprehensive Cancer Center · USUniversity of California, San Francisco · US

Funding

TUMOR SUPPRESOR GENE PROMOTER HYPERMETHYLATION FOR DETECTION OF HEAD AND NECKP50DE019032 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI WESTRA, WILLIAM H · 2007 to 2016
$27.1M
Integrative Pathway Analysis of Eqigenomic/transcriptional Alteration in HNSCCRC1DE020324 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI CALIFANO, JOSEPH A · 2009 to 2010
$918k
Modeling Transcriptional Reprogramming by Markov Chain Monte Carlo SamplingR01LM011000 · NLM · JOHNS HOPKINS UNIVERSITY · PI OCHS, MICHAEL F · 2012 to 2014
$886k
Identifying Malignant Cell Signaling from Protein Interactions an Polyomic DataK25CA141053 · NCI · JOHNS HOPKINS UNIVERSITY · PI FERTIG, ELANA · 2010 to 2014
$419k
NCI NIH HHS CA1410503NIDCR NIH HHS 5P50DE019032NIDCR NIH HHS DE020324NIDCR NIH HHS P50 DE019032NIDCR NIH HHS RC1 DE020324NLM NIH HHS LM001100
6 · The paper itself

Abstract

Head and neck squamous cell carcinoma (HNSCC) is largely divided into two groups based on their etiology, human papillomavirus (HPV)-positive and -negative. Global DNA methylation changes are known to drive oncogene and tumor suppressor expression in primary HNSCC of both types. However, significant heterogeneity in DNA methylation within the groups results in different transcriptional profiles and clinical outcomes. We applied a meta-pathway analysis to link gene expression changes to DNA methylation in distinguishing HNSCC subtypes. This approach isolated specific epigenetic changes controlling expression in HPV- HNSCC that distinguish it from HPV+ HNSCC. Analysis of genes identified Hedgehog pathway activation specific to HPV- HNSCC. We confirmed that GLI1, the primary Hedgehog target, showed higher expression in tumors compared to normal samples with HPV- tumors having the highest GLI1 expression, suggesting that increased expression of GLI1 is a potential driver in HPV- HNSCC. Our algorithm for integration of DNA methylation and gene expression can infer biologically significant molecular pathways that may be exploited as therapeutics targets. Our results suggest that therapeutics targeting the Hedgehog pathway may be of benefit in HPV- HNSCC. Similar integrative analysis of high-throughput coupled DNA methylation and expression datasets may yield novel insights into deregulated pathways in other cancers.

Indexed as

Epigenesis, GeneticGene Expression Regulation, NeoplasticCarcinoma, Squamous CellCluster AnalysisDNA MethylationDNA, NeoplasmFemaleHead and Neck NeoplasmsHedgehog ProteinsHumansMaleNeoplasm StagingOligonucleotide Array Sequence AnalysisPapillomaviridaePapillomavirus InfectionsSignal TransductionDNA, NeoplasmGLI1 protein, humanHedgehog ProteinsTranscription FactorsZinc Finger Protein GLI1

Identifiers

PMID24223768
PMCPMC3817178
OpenAlexW2001895044

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.