Evidence map›Paper›PMID 26093488›Full record

ArticleThe Journal of thoracic and cardiovascular surgery2015

The role of Dickkopf-3 overexpression in esophageal adenocarcinoma.

Zhuwen Wang, Lin Lin, Dafydd G Thomas, Ernest Nadal, Andrew C Chang, David G Beer, Jules Lin

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of thoracic and cardiovascular surgery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

23 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Molecular mechanisms associated with chemoresistance in esophageal cancer.Cellular and molecular life sciences : CMLS · 2022
    Review
  8. Review
  9. Article
  10. Article
  11. Construction and Evaluation of a Risk Score Model for Autophagy-Related Genes in Esophageal Adenocarcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2021
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Dickkopf Homolog 3Frontiers in oncology · 2019
    Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Zhuwen WangSection of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Mich.
Lin LinSection of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Mich.
Dafydd G ThomasDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Mich.
Ernest NadalSection of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Mich.
Andrew C ChangSection of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Mich.
David G BeerSection of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Mich.
Jules LinSection of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Mich. Electronic address: juleslin@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Validation & Pathology CoreU54CA163059 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RUBENSTEIN, JOEL H, WANG, THOMAS D · 2011 to 2022
$12.1M
MOLECULAR STUDIES OF ESOPHAGEAL ADENOCARCINOMAR01CA071606 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BEER, DAVID GEORGE · 1997 to 2009
$3.1M
NCI NIH HHS R01 CA071606NCI NIH HHS U54 CA163059
6 · The paper itself

Abstract

objectivesNinety percent of patients with esophageal adenocarcinoma ultimately die of their disease, highlighting the need for novel therapeutic targets. The goal of this study was to define the functional significance of overexpression of Dickkopf-3 (DKK3) in esophageal adenocarcinoma.

methodsDKK3 expression was analyzed by real-time polymerase chain reaction in 95 chemonaive and 21 chemoresistant esophageal adenocarcinomas. The esophageal adenocarcinoma cell line OE33 was stably transfected with DKK3 (OE33/DKK3) and evaluated using WST-1 (Roche, Basel, Switzerland), Matrigel (BD Biosciences, San Jose, Calif), endothelial tube formation, and chemosensitivity assays. Tumorigenesis was evaluated by injecting 1 × 10(6) OE33/DKK3 and vector cells in NOD/SCIDγ mice.

resultsDKK3 was overexpressed (>2-fold) in 75.8% (72/95) of esophageal adenocarcinomas. DKK3 protein was present at moderate to high levels in 46.8% (29/62) of esophageal adenocarcinomas on tissue microarray. Stable transfection of DKK3 significantly increased proliferation (P < .05) and Matrigel invasion (P < .001). Levels of SMAD4, a key mediator of the transforming growth factor-ß pathway, increased after activin treatment of OE33/DKK3, and siSMAD4 significantly decreased Matrigel invasion, suggesting that DKK3 acts through the transforming growth factor-β pathway. OE33/DKK3 cells increased endothelial tube formation and were significantly more resistant to 5-fluorouracil and cisplatin, and DKK3 expression was significantly higher in chemoresistant esophageal adenocarcinomas (P < .005). In NOD/SCIDγ mice, OE33/DKK3 cells resulted in tumors at all sites (8/8), whereas vector cells grew in only 1 of 8 sites. Nodal metastases were also significantly increased in patients with esophageal adenocarcinomas highly overexpressing DKK3, 28 of 32 (88%) versus 42 of 63 (68%) (P < .05).

conclusionsThese findings suggest that DKK3 may be important in mediating invasion in esophageal adenocarcinoma and could be a novel target in the treatment and prevention of metastatic disease.

Indexed as

Adaptor Proteins, Signal TransducingAdenocarcinomaAnimalsCell Line, TumorCell MovementCell ProliferationChemokinesCoculture TechniquesDrug Resistance, NeoplasmEndothelial CellsEsophageal NeoplasmsGene Expression Regulation, NeoplasticHumansIntercellular Signaling Peptides and ProteinsLymphatic MetastasisMice, Inbred NODAdaptor Proteins, Signal TransducingChemokinesDKK3 protein, humanIntercellular Signaling Peptides and ProteinschemoresistanceDickkopf-3DKK3Esophageal adenocarcinomatissue invasion

Identifiers

PMID26093488
PMCPMC4515149
OpenAlexW2165243775

What OpenQuestion holds

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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.