Evidence map›Paper›PMID 36944688›Full record

SynthesisScientific reports2023

TRAF6 as a potential target in advanced breast cancer: a systematic review, meta-analysis, and bioinformatics validation.

Feier Zeng, Giovana Carrasco, Boya Li, Antonia Sophocleous, Aymen I Idris

Open access · goldFull text readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. 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 2 institutions in 2 countries.

Feier ZengDepartment of Oncology and Metabolism, Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.
Giovana CarrascoDepartment of Oncology and Metabolism, Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.
Boya LiDepartment of Oncology and Metabolism, Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.
Antonia SophocleousDepartment of Life Sciences, School of Sciences, European University Cyprus, 6 Diogenes Street, 1516, Nicosia, Cyprus.
Aymen I IdrisDepartment of Oncology and Metabolism, Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. aymen.idris@sheffield.ac.uk.
University of Sheffield · GBEuropean University Cyprus · CY

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TRAF6 has emerged as a key regulator of breast cancer (BCa). However, the TRAF family constitutes of seven members that exhibit distinct and overlapping functions. To explore which TRAF represents a potential druggable target for BCa treatment, we searched Medline, Web of Science and Scopus for relevant studies from inception to June 27, 2021. We identified 14 in vitro, 11 in vivo and 4 human articles. A meta-analysis of pharmacological studies showed that in vitro inhibition of TRAF2/4 (mean difference (MD): - 57.49, 95% CI: - 66.95, - 48.02, P < 0.00001) or TRAF6 (standard(Std.)MD: - 4.01, 95% CI: - 5.75, - 2.27, P < 0.00001) is associated with reduction in BCa cell migration. Consistently, inhibition of TRAF2/4 (MD: - 51.08, 95% CI: - 64.23, - 37.94, P < 0.00001) and TRAF6 (Std.MD: - 2.80, 95% CI: - 4.26, - 1.34, P = 0.0002) is associated with reduced BCa cell invasion, whereas TRAF2/4 inhibition (MD: - 40.54, 95% CI: - 52.83, - 28.26, P < 0.00001) is associated with reduced BCa cell adhesion. Interestingly, only inhibition of TRAF6 (MD: - 21.46, 95% CI: - 30.40, - 12.51, P < 0.00001) is associated with reduced cell growth. In animal models of BCa, administration of pharmacological inhibitors of TRAF2/4 (Std.MD: - 3.36, 95% CI: - 4.53, - 2.18, P < 0.00001) or TRAF6 (Std.MD: - 4.15, 95% CI: - 6.06, - 2.24, P < 0.0001) in mice is associated with reduction in tumour burden. In contrast, TRAF6 inhibitors (MD: - 2.42, 95% CI: - 3.70, - 1.14, P = 0.0002) reduced BCa metastasis. In BCa patients, high expression of TRAF6 (Hazard Ratio: 1.01, CI: 1.01, 1.01, P < 0.00001) is associated with poor survival rate. Bioinformatics validation of clinical and pathway and process enrichment analysis in BCa patients confirmed that gain/amplification of TRAF6 is associated with secondary BCa in bone (P = 0.0079), and poor survival rate (P < 0.05). Overall, TRAF6 inhibitors show promise in the treatment of metastatic BCa. However, low study number and scarcity of evidence from animal and human studies may limit the translation of present findings into clinical practice.

Indexed as

Breast NeoplasmsTNF Receptor-Associated Factor 6AnimalsFemaleHumansIntracellular Signaling Peptides and ProteinsMiceTNF Receptor-Associated Factor 2Ubiquitin-Protein LigasesIntracellular Signaling Peptides and ProteinsTifab protein, humanTNF Receptor-Associated Factor 2TNF Receptor-Associated Factor 6Ubiquitin-Protein Ligases

Identifiers

PMID36944688
PMCPMC10029787
OpenAlexW4353020455

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read102
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.