Evidence map›Paper›PMID 31165373›Full record

ArticleBreast cancer research and treatment2019

Neuronatin is a modifier of estrogen receptor-positive breast cancer incidence and outcome.

Cody Plasterer, Shirng-Wern Tsaih, Amy R Peck, Inna Chervoneva, Caitlin O'Meara, Yunguang Sun, Angela Lemke, Dana Murphy, Jennifer Smith, Sophia Ran and 11 more

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

Article in Breast cancer research and treatment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.2field-weighted citation impact, top 42% 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

4 citing papers in PubMed, 17 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

21 authors at 7 institutions in 1 country.

Cody PlastererGenomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA.
Shirng-Wern TsaihGenomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA.
Amy R PeckDepartment of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.
Inna ChervonevaDivision of Biostatistics, Thomas Jefferson University, Philadelphia, PA, USA.
Caitlin O'MearaGenomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA.
Yunguang SunDepartment of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.
Angela LemkeGenomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA.
Dana MurphyGenomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA.
Jennifer SmithGenomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA.
Sophia RanSimmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, USA.
Albert J KovatichJohn P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
Jeffrey A HookeJohn P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
Craig D ShriverJohn P. Murtha Cancer Center, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
Hai HuChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Edith P MitchellMedical Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
Carmen BergomDepartment of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
Amit JoshiDepartment of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Paul AuerJoseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
Jeremy ProkopDepartment of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Lansing, MI, USA.
Hallgeir RuiDepartment of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.
Michael J FlisterGenomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA. mflister@mcw.edu.ORCID http://orcid.org/0000-0001-8030-7739
Medical College of Wisconsin · USWalter Reed National Military Medical Center · USThomas Jefferson University · USMichigan State University · USSouthern Illinois University School of Medicine · USUniversity of Wisconsin–Milwaukee · USWindber Research Institute · US

Funding

Leveraging genetic mapping for personalized targeting of breast cancer microenvironmentR01CA193343 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI Amit Joshi · 2015 to 2026
$3.5M
Prolactin pathways and metastatic progression of ER-positive breast cancerR01CA188575 · NCI · THOMAS JEFFERSON UNIVERSITY · PI RUI, HALLGEIR · 2015 to 2019
$1.8M
Clinical and Translational Science AwardKL2TR000056 · NCATS · MEDICAL COLLEGE OF WISCONSIN · PI SHAKER, REZA NONE · 2012 to 2015
$609k
Using a Sequence-to-Structure-to-Function Approach to Functionally Characterize Protein Coding Missense Mutations in the Human and Rat GenomesK01ES025435 · NIEHS · MICHIGAN STATE UNIVERSITY · PI PROKOP, JEREMY WILLIAM · 2014 to 2018
$489k
NCATS NIH HHS KL2 TR000056NCI NIH HHS R01 CA188575NCI NIH HHS R01 CA193343NIEHS NIH HHS K01 ES025435NIH HHS K01ES025435NIH HHS R01CA188575NIH HHS R01CA193343
6 · The paper itself

Abstract

purposeUnderstanding the molecular mediators of breast cancer survival is critical for accurate disease prognosis and improving therapies. Here, we identified Neuronatin (NNAT) as a novel antiproliferative modifier of estrogen receptor-alpha (ER+) breast cancer. EXPERIMENTAL

designGenomic regions harboring breast cancer modifiers were identified by congenic mapping in a rat model of carcinogen-induced mammary cancer. Tumors from susceptible and resistant congenics were analyzed by RNAseq to identify candidate genes. Candidates were prioritized by correlation with outcome, using a consensus of three breast cancer patient cohorts. NNAT was transgenically expressed in ER+ breast cancer lines (T47D and ZR75), followed by transcriptomic and phenotypic characterization.

resultsWe identified a region on rat chromosome 3 (142-178 Mb) that modified mammary tumor incidence. RNAseq of the mammary tumors narrowed the candidate list to three differentially expressed genes: NNAT, SLC35C2, and FAM210B. NNAT mRNA and protein also correlated with survival in human breast cancer patients. Quantitative immunohistochemistry of NNAT protein revealed an inverse correlation with survival in a univariate analysis of patients with invasive ER+ breast cancer (training cohort: n = 444, HR = 0.62, p = 0.031; validation cohort: n = 430, HR = 0.48, p = 0.004). NNAT also held up as an independent predictor of survival after multivariable adjustment (HR = 0.64, p = 0.038). NNAT significantly reduced proliferation and migration of ER+ breast cancer cells, which coincided with altered expression of multiple related pathways.

conclusionsCollectively, these data implicate NNAT as a novel mediator of cell proliferation and migration, which correlates with decreased tumorigenic potential and prolonged patient survival.

Indexed as

Genes, ModifierAnimalsBiomarkers, TumorBreast NeoplasmsCell Line, TumorDisease Models, AnimalFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunohistochemistryIncidenceKaplan-Meier EstimateMembrane ProteinsNeoplasm StagingNerve Tissue ProteinsBiomarkers, TumorMembrane ProteinsNerve Tissue ProteinsNNAT protein, humanReceptors, EstrogenBreast CancerCell cycleEstrogenNNATPrognosis

Identifiers

PMID31165373
PMCPMC10317546
OpenAlexW2948160980

What OpenQuestion holds

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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.