Evidence map›Paper›PMID 24886209›Full record

ArticleBMC cancer2014

Investigation of HOXA9 promoter methylation as a biomarker to distinguish oral cancer patients at low risk of neck metastasis.

Kenichiro Uchida, Ratna Veeramachaneni, Bing Huey, Aditi Bhattacharya, Brian L Schmidt, Donna G Albertson

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Review
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  4. Article
  5. Review
  6. Article
  7. Methylation inCells · 2020
    Review
  8. Oncogenic and tumor suppressor function of MEIS and associated factors.Turkish journal of biology = Turk biyoloji dergisi · 2020
    Article
  9. Article
  10. Article
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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

6 authors at 3 institutions in 2 countries.

Kenichiro Uchida
Ratna Veeramachaneni
Bing Huey
Aditi Bhattacharya
Brian L Schmidt
Donna G AlbertsonHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 Third Street, San Francisco CA 94158-9001, USA. da66@nyu.edu.
UCSF Helen Diller Family Comprehensive Cancer Center · USUniversity of California, San Francisco · USYamaguchi University Hospital · JP

Funding

Amplicons in Oral DysplasiaR01CA131286 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALBERTSON, DONNA G · 2008 to 2011
$1.1M
Genomic and Functional Analysis of Oral Cancer DevelopmentR01CA118323 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALBERTSON, DONNA G · 2007 to 2009
$810k
Predictive Markers for Oral Carcinoma MetastasisR01CA113833 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SCHMIDT, BRIAN L · 2006 to 2008
$804k
NCI NIH HHS CA113833NCI NIH HHS CA118323NCI NIH HHS CA131286
6 · The paper itself

Abstract

backgroundMetastasis to the cervical (neck) lymph nodes is one of the most significant clinical factors responsible for death from oral squamous cell carcinoma (SCC). Therefore, the lymph nodes are frequently removed when the tumor is excised (neck dissection), even though the majority of patients will not benefit from the extra surgery. Two subtypes of oral SCC distinguished by the presence of tumor genomic aberrations +3q, -8p, +8q and/or +20 differ in risk for metastasis - high for the 3q8pq20 subtype, harboring one or more of the aberrations and low for the non-3q8pq20 subtype, lacking these alterations. A prior analysis of the literature suggested genes differentially methylated in the two subtypes. Therefore, the goal of this study was to further investigate the methylation status of candidate biomarkers of the non-3q8pq20 subtype, and evaluate their utility for identifying patients at low risk for metastasis.

methodsMethylation status of genes in a cohort of 52 oral SCC patients with at least five year follow up was determined by pyrosequencing. Gene expression levels were determined by quantitative RT-PCR. Growth following re-expression of HOXA9 in cultured oral SCC cells was assessed by proliferation and colony formation assays.

resultsA pilot study evaluating methylation levels of HOXA9, MT1A and HOXA11 promoters in DNA from 12 tumors (six each of the 3q8pq20 and non-3q8pq20 subtypes) revealed that only HOXA9 was differentially methylated. Significant differences in methylation levels of HOXA9 were observed amongst the 52 oral SCCs with respect to genomic subtype and nodal status (p = 0.014, and p = 0.024, respectively, Wilcoxon rank sum test). High levels of HOXA9 methylation and low levels of expression in oral SCC cell lines were observed compared to HaCaT, a non-tumorigenic keratinocyte cell line. Re-expression of HOXA9 in the SCC4 oral cancer cell line resulted in diminished proliferation and colony formation.

conclusionsHOXA9 methylation is frequent in oral cancers and levels are higher in tumors with greater risk of metastasis. Expression of HOXA9 is low in cells with high levels of methylation and reduced expression appears to confer a growth advantage.

Indexed as

DNA MethylationPromoter Regions, GeneticBiomarkers, TumorCarcinoma, Squamous CellCell Line, TumorCell ProliferationHomeodomain ProteinsHumansLymphatic MetastasisMouth NeoplasmsPilot ProjectsRisk AssessmentRisk FactorsTime FactorsTransfectionBiomarkers, Tumorhomeobox protein HOXA9Homeodomain Proteins

Identifiers

PMID24886209
PMCPMC4045880
OpenAlexW1987727129

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.