Evidence map›Paper›PMID 36576731›Full record

ArticleTranslational vision science & technology2022

Investigating the Role of DUSP4 in Uveal Melanoma.

Karen Aughton, Dorota Sabat-Pospiech, Samantha Barlow, Sarah E Coupland, Helen Kalirai

Open access · goldAbstract read
In one paragraph

Article in Translational vision science & technology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Frontiers in microbiology · 2025
    Article
  2. siRNA-based strategies to combat drug resistance in gastric cancer.Medical oncology (Northwood, London, England) · 2024
    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

5 authors at 1 institution in 1 country.

Karen AughtonLiverpool Ocular Oncology Research Group, University of Liverpool, Molecular and Clinical Cancer Medicine, Institute of Systems Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
Dorota Sabat-PospiechLiverpool Ocular Oncology Research Group, University of Liverpool, Molecular and Clinical Cancer Medicine, Institute of Systems Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
Samantha BarlowLiverpool Ocular Oncology Research Group, University of Liverpool, Molecular and Clinical Cancer Medicine, Institute of Systems Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
Sarah E CouplandLiverpool Ocular Oncology Research Group, University of Liverpool, Molecular and Clinical Cancer Medicine, Institute of Systems Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
Helen KaliraiLiverpool Ocular Oncology Research Group, University of Liverpool, Molecular and Clinical Cancer Medicine, Institute of Systems Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
University of Liverpool · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Dual-specificity phosphatase 4 (DUSP4) inactivates factors in the mitogen-activated protein kinase (MAPK) signaling cascade, activated in uveal melanoma (UM) by mutations in upstream G-protein α subunits GNAQ/11 in >90% cases. This study examined whether DUSP4 (1) protein expression in primary UM (pUM) was a biomarker of metastatic risk and (2) knockdown sensitized UM cells to therapeutic agents, selumetinib or doxorubicin. Methods: DUSP4 mRNA data from The Cancer Genome Atlas and DUSP4 protein expression examined using immunohistochemistry in 28 cases of pUM were evaluated for association with clinical, genetic, and histological features. In vitro cytotoxic drug assays tested the efficacy of selumetinib and doxorubicin in UM cell lines with/without small interfering RNA DUSP4 gene silencing. Results: DUSP4 protein expression was observed in 93% of cases, with strong nuclear positivity in 79%. Despite higher DUSP4 messenger RNA levels in disomy 3/wild-type BAP1 UM, there was no significant association of nDUSP4 protein with these metastatic risk predictors or outcome. DUSP4 expression in UM cell lines varied. DUSP4 silencing in Mel202, MP46, and MP41 cells did not affect ERK1/2 or phospho-ERK levels. Despite increased phospho-ERK levels in Mel285, no cell line showed enhanced sensitivity to selumetinib/doxorubicin. Conclusions: DUSP4 protein expression is not a biomarker of UM metastatic risk. DUSP4 plays a complex role in oncogenesis, as reported in other cancers, and further work is required to fully understand its functional role in the MAPK pathway. Translational Relevance: Understanding the role of phosphatases, such as DUSP4, in the control of intracellular signaling cascades will facilitate our ability to identify successful treatment options.

Indexed as

MelanomaUveal NeoplasmsDoxorubicinDual-Specificity PhosphatasesHumansMitogen-Activated Protein Kinase PhosphatasesUveal MelanomaDoxorubicinDual-Specificity PhosphatasesDUSP4 protein, humanMitogen-Activated Protein Kinase Phosphatases

Identifiers

PMID36576731
PMCPMC9804032
OpenAlexW4313417290

What Socratic holds

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LicenceCC BY
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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 Socratic graph.