Evidence map›Paper›PMID 23174249›Full record

ArticleThe Journal of urology2013

CpG island hypermethylation frequently silences FILIP1L isoform 2 expression in prostate cancer.

Joshua Desotelle, Matthew Truong, Jonathan Ewald, Pushpa Weeratunga, Bing Yang, Wei Huang, David Jarrard

Open access · greenAbstract read
In one paragraph

Article in The Journal of urology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 22% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Promoter Methylation ofInternational journal of molecular sciences · 2021
    Article
  5. Article
  6. Article
  7. Article
  8. Clinical and Novel Biomarkers in the Management of Prostate Cancer.Current treatment options in oncology · 2018
    Review
  9. Tissue-based biomarkers in prostate cancer.Expert review of precision medicine and drug development · 2017
    Article
  10. Article
  11. Article
  12. Biomarkers in localized prostate cancer.Future oncology (London, England) · 2016
    Review
  13. Article
  14. Article
  15. Biomarkers in prostate cancer: what's new?Current opinion in oncology · 2014
    Review
  16. Article
  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Joshua DesotelleDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Wisconsin, USA.
Matthew Truong
Jonathan Ewald
Pushpa Weeratunga
Bing Yang
Wei Huang
David Jarrard
University of Wisconsin–Madison · USUniversity of Wisconsin Carbone Cancer Center · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
MODULATION OF IGF-II IMPRINTING IN THE AGING PROSTATER01CA097131 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI JARRARD, DAVID F. · 2002 to 2013
$2.5M
NCI NIH HHS 5R01CA097131NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA097131
6 · The paper itself

Abstract

purposeSenescence related regulatory pathways serve as barriers to cancer immortalization and progression but they are currently not well defined. FILIP1L is a growth inhibitory gene with multiple isoforms whose expression is increased in senescent prostate and prostate cancer cells, and decreased in many cancers. We investigated whether DNA methylation regulates FILIP1L in senescence and in prostate cancer development. MATERIALS AND

methodsFILIP1L mRNA expression was assessed in prostate cancer and associated normal prostate tissues using quantitative polymerase chain reaction. A tissue microarray was constructed using 95 prostate cancer specimens and 45 benign prostate specimens. Vectra™ imaging was used to quantitate nuclear and cytoplasmic FILIP1L protein expression. Bisulfite sequencing and Pyrosequencing® were used to assess methylation. Prostate cancer cell lines were treated with 2'-deoxy-5-azacytidine and mRNA expression was assessed.

resultsFILIP1L isoform 2 mRNA was increased in replicatively senescent human prostate epithelial cells and decreased in prostate cancer specimens. We verified a reduction in nuclear FILIP1L protein in prostate cancer using tissue microarrays (p = 0.006). A CpG island 5' of the isoform 2 translational start site was identified that showed hypermethylation in prostate cancer cell lines and tumors compared to normal prostate cells and tissues. Pyrosequencing confirmed FILIP1L hypermethylation in all 14 tumors compared to paired normal tissues (p <0.0001). Isoform 2 expression was induced in prostate cancer cell lines using 2'-deoxy-5-azacytidine.

conclusionsFILIP1L isoform 2 is one of the most commonly hypermethylated genes in prostate cancer. It may serve as an important marker of prostate cancer. Isoform 2 expression is associated with senescence and its down-regulation may represent an early important biological event in prostate cancer development.

Indexed as

DNA MethylationGene Expression Regulation, NeoplasticGene SilencingCarrier ProteinsCells, CulturedCellular SenescenceCpG IslandsCytoskeletal ProteinsHumansMaleProstatic NeoplasmsProtein IsoformsCarrier ProteinsCytoskeletal ProteinsFILIP1 protein, humanProtein Isoforms

Identifiers

PMID23174249
PMCPMC3581042
OpenAlexW2094466263

What OpenQuestion holds

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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.