Evidence map›Paper›PMID 28632792›Full record

ArticlePloS one2017

Identification of cell proliferation, immune response and cell migration as critical pathways in a prognostic signature for HER2+:ERα- breast cancer.

Jeffrey C Liu, Miriam Zacksenhouse, Andrea Eisen, Sharon Nofech-Mozes, Eldad Zacksenhaus

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-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

6 citing papers in PubMed, 11 citations in OpenAlex.

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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.

Jeffrey C LiuDivision of Advanced Diagnostics, Toronto General Research Institute-University Health Network, Toronto, Ontario, Canada.
Miriam ZacksenhouseBrain-computer Interfaces for Rehabilitation Laboratory, Faculty of Mechanical Engineering, Technion-Israel Institute of Technology Haifa, Israel.
Andrea EisenSunnybrook Health Sciences Centre, University of Toronto; Toronto, Ontario, Canada.
Sharon Nofech-MozesSunnybrook Health Sciences Centre, University of Toronto; Toronto, Ontario, Canada.
Eldad ZacksenhausDivision of Advanced Diagnostics, Toronto General Research Institute-University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-6104-6094
Sunnybrook Health Science Centre · CAUniversity Health Network · CATechnion – Israel Institute of Technology · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMulti-gene prognostic signatures derived from primary tumor biopsies can guide clinicians in designing an appropriate course of treatment. Identifying genes and pathways most essential to a signature performance may facilitate clinical application, provide insights into cancer progression, and uncover potentially new therapeutic targets. We previously developed a 17-gene prognostic signature (HTICS) for HER2+:ERα- breast cancer patients, using genes that are differentially expressed in tumor initiating cells (TICs) versus non-TICs from MMTV-Her2/neu mammary tumors. Here we probed the pathways and genes that underlie the prognostic power of HTICS.

methodsWe used Leave-One Out, Data Combination Test, Gene Set Enrichment Analysis (GSEA), Correlation and Substitution analyses together with Receiver Operating Characteristic (ROC) and Kaplan-Meier survival analysis to identify critical biological pathways within HTICS. Publically available cohorts with gene expression and clinical outcome were used to assess prognosis. NanoString technology was used to detect gene expression in formalin-fixed paraffin embedded (FFPE) tissues.

resultsWe show that three major biological pathways: cell proliferation, immune response, and cell migration, drive the prognostic power of HTICS, which is further tuned by Homeostatic and Glycan metabolic signalling. A 6-gene minimal Core that retained a significant prognostic power, albeit less than HTICS, also comprised the proliferation/immune/migration pathways. Finally, we developed NanoString probes that could detect expression of HTICS genes and their substitutions in FFPE samples.

conclusionOur results demonstrate that the prognostic power of a signature is driven by the biological processes it monitors, identify cell proliferation, immune response and cell migration as critical pathways for HER2+:ERα- cancer progression, and defines substitutes and Core genes that should facilitate clinical application of HTICS.

Indexed as

Critical PathwaysBreast NeoplasmsCell MovementCell ProliferationErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunity, CellularNeoplastic Stem CellsPrognosisERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesESR1 protein, humanEstrogen Receptor alpha

Identifiers

PMID28632792
PMCPMC5478114
OpenAlexW2715305028

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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.