Evidence map›Paper›PMID 25961636›Full record

ArticleEpigenetics2015

Analysis of DNA methylation and gene expression in radiation-resistant head and neck tumors.

Xiaofei Chen, Liang Liu, Jade Mims, Elizabeth C Punska, Kristin E Williams, Weiling Zhao, Kathleen F Arcaro, Allen W Tsang, Xiaobo Zhou, Cristina M Furdui

Open access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

55 citing papers in PubMed, 90 citations in OpenAlex.

  1. Review
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  10. Review
  11. KLF4 is an epigenetically modulated, context-dependent tumor suppressor.Frontiers in cell and developmental biology · 2024
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. [Redox biology · 2022
    Article
  18. 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

10 authors at 5 institutions in 2 countries.

Xiaofei Chena Section on Molecular Medicine; Department of Internal Medicine; Wake Forest School of Medicine ; Winston-Salem , NC , USA.
Liang Liu
Jade Mims
Elizabeth C Punska
Kristin E Williams
Weiling Zhao
Kathleen F Arcaro
Allen W Tsang
Xiaobo Zhou
Cristina M Furdui
Winston-Salem State University · USUniversity of Massachusetts Amherst · USAmherst College · USInstitute of Molecular Medicine · INWake Forest University · US

Funding

Tumor Tissue CoreP30CA012197 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Ruben A. Mesa · 1985 to 2026
$55.4M
Modelling the Growth of the MIC Niche at the System LevelU01CA166886 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ZHOU, XIAOBO · 2012 to 2016
$2.2M
Integrative Lipid Metabolism, Inflammation, and Chronic DiseasesT32HL091797 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI PARKS, JOHN S · 2008 to 2017
$1.8M
Analysis of Redox Modulated Signaling Networks in Response to Ionizing RadiationR01CA136810 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI FURDUI, CRISTINA MARIA · 2009 to 2013
$1.5M
System Biology Approach for Signaling Transduction Study of Complex PhenotypesR01LM010185 · NLM · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ZHOU, XIAOBO, ZU, YOULI · 2009 to 2012
$1.3M
NCI NIH HHS P30CA012197NCI NIH HHS R01 CA136810NCI NIH HHS U01 CA166886NHLBI NIH HHS T32 HL091797NLM NIH HHS R01LM010185
6 · The paper itself

Abstract

Resistance to radiation therapy constitutes a significant challenge in the treatment of head and neck squamous cell cancer (HNSCC). Alteration in DNA methylation is thought to play a role in this resistance. Here, we analyzed DNA methylation changes in a matched model of radiation resistance for HNSCC using the Illumina HumanMethylation450 BeadChip. Our results show that compared to radiation-sensitive cells (SCC-61), radiation-resistant cells (rSCC-61) had a significant increase in DNA methylation. After combining these results with microarray gene expression data, we identified 84 differentially methylated and expressed genes between these 2 cell lines. Ingenuity Pathway Analysis revealed ILK signaling, glucocorticoid receptor signaling, fatty acid α-oxidation, and cell cycle regulation as top canonical pathways associated with radiation resistance. Validation studies focused on CCND2, a protein involved in cell cycle regulation, which was identified as hypermethylated in the promoter region and downregulated in rSCC-61 relative to SCC-61 cells. Treatment of rSCC-61 and SCC-61 with the DNA hypomethylating agent 5-aza-2'deoxycitidine increased CCND2 levels only in rSCC-61 cells, while treatment with the control reagent cytosine arabinoside did not influence the expression of this gene. Further analysis of HNSCC data from The Cancer Genome Atlas found increased methylation in radiation-resistant tumors, consistent with the cell culture data. Our findings point to global DNA methylation status as a biomarker of radiation resistance in HNSCC, and suggest a need for targeted manipulation of DNA methylation to increase radiation response in HNSCC.

Indexed as

AzacitidineCell Line, TumorCpG IslandsCyclin D2DecitabineDNA MethylationGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansKruppel-Like Factor 4Promoter Regions, GeneticRadiation ToleranceAzacitidineCCND2 protein, humanCyclin D2DecitabineKLF4 protein, humanKruppel-Like Factor 45-Aza, 5-aza-2′deoxycitidineAKT, Protein kinase BAraC, Cytosine arabinosideCCNA1, Cyclin A1CCND2, Cyclin D2CDK4, Cyclin-dependent kinase 4CDKN1A, Cyclin-dependent kinase inhibitor 1A (p21, Cip1)dmCpG, differentially methylated CpGDNA methylationDNMT, DNA methyltransferaseEIF2AK2, Eukaryotic translation initiation factor 2-αkinase 2FASN, Fatty acid synthaseGene expressionGSK-3, Glycogen synthase kinase 3Head and neck squamous cell cancer (HNSCC)HM450, HumanMethylation450HNSCC, Head and neck squamous cell cancerhTERT, human telomerase reverse transcriptaseIGFBP3, Insulin-like growth factor-binding protein 3ILK, Integrin linked kinaseIPA, Ingenuity pathway analysisIRF1, Interferon regulatory factor 1KLF4, Kruppel-like factor 4KRT19, Keratin 19, LIPG, Endothelial lipaseLXR, Liver X receptorMGMT, O6-methylguanine DNA methyltransferaseNFATC2, Nuclear factor of activated t-cells cytoplasmic 2PCNA, Proliferating cell nuclear antigenPTEN, Phosphatase and tensin homologRadiation resistanceRXR, Retinoid X receptorSAM, S-AdenosylmethionineSOCS3, Suppressor of cytokine signaling 3STAT1, Signal transducers and activators of transcription 1TCGA, The Cancer Genome AtlasThe Cancer Genome Atlas (TCGA)VHL, Von Hippel–Lindau tumor suppressor

Identifiers

PMID25961636
PMCPMC4622425
OpenAlexW1715707987

What OpenQuestion holds

Textmetadata
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.