Evidence map›Paper›PMID 25084021›Full record

ArticlePloS one2014

EZH2 is associated with malignant behavior in pancreatic IPMN via p27Kip1 downregulation.

Hideyuki Kuroki, Hiromitsu Hayashi, Hirohisa Okabe, Daisuke Hashimoto, Hiroshi Takamori, Osamu Nakahara, Shigeki Nakagawa, Yukiko Fukushima, Akira Chikamoto, Toru Beppu and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 2 pooled it
1.3field-weighted citation impact, top 21% 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

11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Prognostic Value of TWIST1 and EZH2 Expression in Colon Cancer.Journal of gastrointestinal cancer · 2021
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Pancreatic adenocarcinoma pathology: changing "landscape".Journal of gastrointestinal oncology · 2015
    Review
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 2 institutions in 1 country.

Hideyuki KurokiDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hiromitsu HayashiDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hirohisa OkabeDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Daisuke HashimotoDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hiroshi TakamoriDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Osamu NakaharaDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Shigeki NakagawaDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yukiko FukushimaDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Akira ChikamotoDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Toru BeppuDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Masahiko HirotaDepartment of Surgery, Kumamoto Regional Medical Center, Kumamoto, Japan.
Ken-ichi IyamaDepartment of Surgical Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hideo BabaDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Kumamoto University · JPKumamoto Medical Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe epigenetic mechanism of tumorigenesis in pancreatic intraductal papillary mucinous neoplasm (IPMN) remains largely unknown. The aim of this study is to examine the role of enhancer of zeste homologue 2 (EZH2) alteration in pancreatic IPMN progression.

methodsFifty-four surgically resected pancreatic IPMN specimens, including a total of 181 lesions (normal duct in 48, adenoma in 50, borderline atypia in 53, carcinoma in situ (CIS) in 19, and invasive carcinoma in 11) were analyzed by immunohistochemical staining (EZH2, Ki-67, p27Kip1). Using paraffin embedded sections, total RNA was successfully extracted from 20 IPMN lesions (borderline IPMN in 9, CIS in 6, invasive carcinoma in 5) and 7 pancreatic normal ducts, and then levels of EZH2 and p27Kip1 mRNA were analyzed by real time PCR.

resultsIn immunohistochemical analysis, cell proliferative activity revealed by Ki-67 positive nuclei was increased during IPMN progression (normal duct<adenoma<borderline atypia<CIS ≈ invasive carcinoma). EZH2 expression displayed a similar pattern (normal duct<adenoma<borderline atypia<CIS ≈ invasive carcinoma) with cell proliferative activity. EZH2 expression in malignant (CIS and invasive carcinoma) IPMNs was significantly higher than that in adenoma and borderline-atypia IPMNs. EZH2 expression level in IPMN lesions was positively correlated with the Ki-67 positive nuclear ratio (p<0.0001). EZH2-positive cells in malignant IPMN did not express p27Kip1. EZH2 mRNA expressions in malignant lesions were significantly higher than those in benign lesions (p<0.0001). In contrast, p27Kip1 mRNA in malignant lesions was significantly decreased compared to those in benign lesion (p<0.05), and there was an inverse correlation between EZH2 and p27Kip1 mRNA levels (p = 0.0109).

conclusionEZH2 is associated with the accelerated cell proliferation and malignant step in pancreatic IPMN via the downregulation of p27Kip1.

Indexed as

Adenocarcinoma, MucinousAgedCarcinoma, Pancreatic DuctalCarcinoma, PapillaryCell ProliferationCyclin-Dependent Kinase Inhibitor p27Disease ProgressionDown-RegulationEnhancer of Zeste Homolog 2 ProteinFemaleGene ExpressionHumansImmunohistochemistryMaleMiddle AgedNeoplasm GradingBMI1 protein, humanCyclin-Dependent Kinase Inhibitor p27Enhancer of Zeste Homolog 2 ProteinEZH2 protein, humanPolycomb Repressive Complex 1Polycomb Repressive Complex 2

Identifiers

PMID25084021
PMCPMC4118850
OpenAlexW1978667789

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Registered trials

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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.