Evidence map›Paper›PMID 31138829›Full record

ArticleScientific reports2019

PCA-PAM50 improves consistency between breast cancer intrinsic and clinical subtyping reclassifying a subset of luminal A tumors as luminal B.

Praveen-Kumar Raj-Kumar, Jianfang Liu, Jeffrey A Hooke, Albert J Kovatich, Leonid Kvecher, Craig D Shriver, Hai Hu

Open access · goldAbstract read
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 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

  1. Pooled it
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  17. The Transcriptomic Landscape of Pediatric Astrocytoma.International journal of molecular sciences · 2022
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  18. Review
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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

7 authors at 2 institutions in 1 country.

Praveen-Kumar Raj-KumarChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.ORCID http://orcid.org/0000-0001-6596-9283
Jianfang LiuChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Jeffrey A HookeClinical Breast Care Project, Murtha Cancer Center Research Program, Uniformed Services University of Health Sciences/Walter Reed National Military Medical Center, Bethesda, MD, USA.
Albert J KovatichClinical Breast Care Project, Murtha Cancer Center Research Program, Uniformed Services University of Health Sciences/Walter Reed National Military Medical Center, Bethesda, MD, USA.
Leonid KvecherChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA.
Craig D ShriverMurtha Cancer Center Research Program, Uniformed Services University of Health Sciences/Walter Reed National Military Medical Center, Bethesda, MD, USA.
Hai HuChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA. H.Hu@wriwindber.org.
Windber Research Institute · USWalter Reed National Military Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The PAM50 classifier is widely used for breast tumor intrinsic subtyping based on gene expression. Clinical subtyping, however, is based on immunohistochemistry assays of 3-4 biomarkers. Subtype calls by these two methods do not completely match even on comparable subtypes. Nevertheless, the estrogen receptor (ER)-balanced subset for gene-centering in PAM50 subtyping, is selected based on clinical ER status. Here we present a new method called Principle Component Analysis-based iterative PAM50 subtyping (PCA-PAM50) to perform intrinsic subtyping in ER status unbalanced cohorts. This method leverages PCA and iterative PAM50 calls to derive the gene expression-based ER status and a subsequent ER-balanced subset for gene centering. Applying PCA-PAM50 to three different breast cancer study cohorts, we observed improved consistency (by 6-9.3%) between intrinsic and clinical subtyping for all three cohorts. Particularly, a more aggressive subset of luminal A (LA) tumors as evidenced by higher MKI67 gene expression and worse patient survival outcomes, were reclassified as luminal B (LB) increasing the LB subtype consistency with IHC by 25-49%. In conclusion, we show that PCA-PAM50 enhances the consistency of breast cancer intrinsic and clinical subtyping by reclassifying an aggressive subset of LA tumors into LB. PCA-PAM50 code is available at ftp://ftp.wriwindber.org/ .

Indexed as

Biomarkers, TumorBreast NeoplasmsCohort StudiesErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaFemaleGene ExpressionGene Expression ProfilingHumansImmunohistochemistryKi-67 AntigenPrincipal Component AnalysisPrognosisProtein Array AnalysisSurvival AnalysisTerminology as TopicBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesESR1 protein, humanEstrogen Receptor alphaKi-67 AntigenMKI67 protein, human

Identifiers

PMID31138829
PMCPMC6538748
OpenAlexW2947669958

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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.