Evidence map›Paper›PMID 26634247›Full record

ArticleMolecular cancer2015

Impaired aldehyde dehydrogenase 1 subfamily member 2A-dependent retinoic acid signaling is related with a mesenchymal-like phenotype and an unfavorable prognosis of head and neck squamous cell carcinoma.

Katharina Seidensaal, Andre Nollert, Agnes Hiou Feige, Marie Muller, Thomas Fleming, Nikolas Gunkel, Karim Zaoui, Niels Grabe, Wilko Weichert, Klaus-Josef Weber and 3 more

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

Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

20 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. The Influences of RARγ on the Behavior of Normal and Cancer Stem Cells.International journal of molecular sciences · 2026
    Review
  3. Article
  4. Review
  5. Deregulation of All-International journal of molecular sciences · 2023
    Review
  6. Review
  7. Targeting the Retinoic Acid Pathway to Eradicate Cancer Stem Cells.International journal of molecular sciences · 2023
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Interactions between tumor mutation burden and immune infiltration in ovarian cancer.International journal of clinical and experimental pathology · 2020
    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

13 authors at 3 institutions in 2 countries.

Katharina SeidensaalDepartment of Otolaryngology, Head and Neck Surgery, Section Experimental and Translational Head and Neck Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, D-69120, Heidelberg, Germany. k.seidensaal@yahoo.de.
Andre NollertDepartment of Otolaryngology, Head and Neck Surgery, Section Experimental and Translational Head and Neck Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, D-69120, Heidelberg, Germany. andre.nollert@gmx.de.
Agnes Hiou FeigeService d'Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Centre Hospitalier Universitaire Vaudois (CHUV), Université Lausanne, Lausanne, Switzerland. agnes.hiou@chuv.ch.
Marie MullerDepartment of Otolaryngology, Head and Neck Surgery, Section Experimental and Translational Head and Neck Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, D-69120, Heidelberg, Germany. marief4@web.de.
Thomas FlemingDepartment of Medicine I and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany. thomas.fleming@med.uni-heidelberg.de.
Nikolas GunkelCancer Drug Discovery, German Cancer Research Center Heidelberg, Heidelberg, Germany. n.gunkel@dkfz-heidelberg.de.
Karim ZaouiDepartment of Otolaryngology, Head and Neck Surgery, Section Experimental and Translational Head and Neck Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, D-69120, Heidelberg, Germany. karim.zaoui@med.uni-heidelberg.de.
Niels GrabeHamamatsu Tissue Imaging and Analysis Center (TIGA), BIOQUANT, Heidelberg, Germany. niels.grabe@bioquant.uni-heidelberg.de.
Wilko WeichertInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. wilko.weichert@tum.de.
Klaus-Josef WeberDepartment of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany. klaus-josef.weber@med.uni-heidelberg.de.
Peter PlinkertDepartment of Otolaryngology, Head and Neck Surgery, Section Experimental and Translational Head and Neck Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, D-69120, Heidelberg, Germany. peter.plinkert@med.uni-heidelberg.de.
Christian SimonService d'Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Centre Hospitalier Universitaire Vaudois (CHUV), Université Lausanne, Lausanne, Switzerland. Christian.Simon@chuv.ch.
Jochen HessDepartment of Otolaryngology, Head and Neck Surgery, Section Experimental and Translational Head and Neck Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, D-69120, Heidelberg, Germany. Jochen.Hess@med.uni-heidelberg.de.
Heidelberg University · DEUniversity Hospital Heidelberg · DEUniversity Hospital of Lausanne · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAn inverse correlation between expression of the aldehyde dehydrogenase 1 subfamily A2 (ALDH1A2) and gene promoter methylation has been identified as a common feature of oropharyngeal squamous cell carcinoma (OPSCC). Moreover, low ALDH1A2 expression was associated with an unfavorable prognosis of OPSCC patients, however the causal link between reduced ALDH1A2 function and treatment failure has not been addressed so far.

methodsSerial sections from tissue microarrays of patients with primary OPSCC (n = 101) were stained by immunohistochemistry for key regulators of retinoic acid (RA) signaling, including ALDH1A2. Survival with respect to these regulators was investigated by univariate Kaplan-Meier analysis and multivariate Cox regression proportional hazard models. The impact of ALDH1A2-RAR signaling on tumor-relevant processes was addressed in established tumor cell lines and in an orthotopic mouse xenograft model.

resultsImmunohistochemical analysis showed an improved prognosis of ALDH1A2(high) OPSCC only in the presence of CRABP2, an intracellular RA transporter. Moreover, an ALDH1A2(high)CRABP2(high) staining pattern served as an independent predictor for progression-free (HR: 0.395, p = 0.007) and overall survival (HR: 0.303, p = 0.002), suggesting a critical impact of RA metabolism and signaling on clinical outcome. Functionally, ALDH1A2 expression and activity in tumor cell lines were related to RA levels. While administration of retinoids inhibited clonogenic growth and proliferation, the pharmacological inhibition of ALDH1A2-RAR signaling resulted in loss of cell-cell adhesion and a mesenchymal-like phenotype. Xenograft tumors derived from FaDu cells with stable silencing of ALDH1A2 and primary tumors from OPSCC patients with low ALDH1A2 expression exhibited a mesenchymal-like phenotype characterized by vimentin expression.

conclusionsThis study has unraveled a critical role of ALDH1A2-RAR signaling in the pathogenesis of head and neck cancer and our data implicate that patients with ALDH1A2(low) tumors might benefit from adjuvant treatment with retinoids.

Indexed as

Aldehyde Dehydrogenase 1 FamilyAnimalsAntineoplastic AgentsCarcinoma, Squamous CellCell AdhesionCell Line, TumorCell ProliferationHead and Neck NeoplasmsHumansKaplan-Meier EstimateMice, NudeNeoplasm TransplantationPhenotypePrognosisProportional Hazards ModelsReceptors, Retinoic AcidAldehyde Dehydrogenase 1 FamilyALDH1A2 protein, humanAntineoplastic AgentsReceptors, Retinoic AcidRetinal Dehydrogenaseretinoic acid binding protein II, cellularTretinoin

Identifiers

PMID26634247
PMCPMC4669670
OpenAlexW2185418047

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.