Evidence map›Paper›PMID 31836816›Full record

ArticleScientific reports2019

Molecular stratification within triple-negative breast cancer subtypes.

Dong-Yu Wang, Zhe Jiang, Yaacov Ben-David, James R Woodgett, Eldad Zacksenhaus

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 2 pooled it
6.8field-weighted citation impact, top 2% 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

88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 149 citations in OpenAlex.

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28 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Dong-Yu WangToronto General Research Institute, University Health Network, 67 College Street, Toronto, Ontario, M5G 2M1, Canada.ORCID http://orcid.org/0000-0002-5434-287X
Zhe JiangToronto General Research Institute, University Health Network, 67 College Street, Toronto, Ontario, M5G 2M1, Canada.
Yaacov Ben-DavidThe Key laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, Guizhou, 550014, China.
James R WoodgettLunenfeld-Tanenbaum Research Institute, Sinai Health System, 600 University Avenue, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-3731-5797
Eldad ZacksenhausToronto General Research Institute, University Health Network, 67 College Street, Toronto, Ontario, M5G 2M1, Canada. eldad.zacksenhaus@utoronto.ca.
University Health Network · CAGuiyang Medical University · CNLunenfeld-Tanenbaum Research Institute · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) has been subdivided into six distinct subgroups: basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M), mesenchymal stem-like (MSL), immunomodulatory (IM), and luminal androgen receptor (LAR). We recently identified a subgroup of TNBC with loss of the tumor suppressor PTEN and five specific microRNAs that exhibits exceedingly poor clinical outcome and contains TP53 mutation, RB1 loss and high MYC and WNT signalling. Here, show that these PTEN-low/miRNA-low lesions cluster with BL1 TNBC. These tumors exhibited high RhoA signalling and were significantly stratified on the basis of PTEN-low/RhoA-signalling-high with hazard ratios (HRs) of 8.2 (P = 0.0009) and 4.87 (P = 0.033) in training and test cohorts, respectively. For BL2 TNBC, we identified AKT1 copy gain/high mRNA expression as surrogate for poor prognosis (HR = 3.9; P = 0.02 and HR = 6.1; P = 0.0032). In IM, programmed cell death 1 (PD1) was elevated and predictive of poor prognosis (HR = 5.3; P = 0.01 and HR = 3.5; P < 0.004). Additional alterations, albeit without prognostic power, characterized each subtype including high E2F2 and TGFβ signalling and CXCL8 expression in BL2, high IFNα and IFNγ signalling and CTLA4 expression in IM, and high EGFR signalling in MSL, and may be targeted for therapy. This study identified PTEN-low/RhoA-signalling-high, and high AKT1 and PD1 expression as potent prognostications for BL1, BL2 and IM subtypes with survival differences of over 14, 2.75 and 10.5 years, respectively. This intrinsic heterogeneity could be exploited to prioritize patients for precision medicine.

Indexed as

Gene Expression ProfilingCluster AnalysisComputational BiologyDatabases, FactualFemaleGene DosageGene Expression Regulation, NeoplasticHumansMicroRNAsPrognosisProto-Oncogene Proteins c-mycPTEN PhosphohydrolaseReceptors, AndrogenRetinoblastoma Binding ProteinsSignal TransductionTreatment OutcomeAR protein, humanMicroRNAsMYC protein, humanProto-Oncogene Proteins c-mycPTEN PhosphohydrolasePTEN protein, humanRB1 protein, humanReceptors, AndrogenRetinoblastoma Binding ProteinsTP53 protein, humanTumor Suppressor Protein p53Ubiquitin-Protein LigasesWnt Proteins

Identifiers

PMID31836816
PMCPMC6911070
OpenAlexW2995712298

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.