Evidence map›Paper›PMID 34725325›Full record

ArticleNature communications2021

Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes.

Brian D Lehmann, Antonio Colaprico, Tiago C Silva, Jianjiao Chen, Hanbing An, Yuguang Ban, Hanchen Huang, Lily Wang, Jamaal L James, Justin M Balko and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed, 1 pooled it
14.5field-weighted citation impact, top 1% 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

171 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.

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111 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

15 authors at 4 institutions in 1 country.

Brian D Lehmann *Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. brian.d.lehmann@vumc.org.ORCID 0000-0003-0407-5248
Antonio Colaprico *Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Tiago C SilvaDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.ORCID 0000-0003-1343-6850
Jianjiao ChenDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.ORCID 0000-0001-5438-3236
Hanbing AnDepartment of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Yuguang BanDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.ORCID 0000-0002-2874-0647
Hanchen HuangDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Lily WangDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Jamaal L JamesDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Justin M BalkoDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.ORCID 0000-0002-4263-5974
Paula I Gonzalez-EricssonVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.ORCID 0000-0002-6292-6963
Melinda E SandersVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Bing ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.ORCID 0000-0001-8676-2425
Jennifer A PietenpolVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
X Steven ChenDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. steven.chen@med.miami.edu.
University of Miami · USVanderbilt University Medical Center · USBaylor College of Medicine · USVanderbilt University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
TISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7M
iPGDAC, An Integrative Proteogenomic Data Analysis Center for CPTACU24CA210954 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, BING · 2016 to 2020
$4.9M
Integrative prediction models for metastasis risk in colon cancerR01CA158472 · NCI · VANDERBILT UNIVERSITY · PI BEAUCHAMP, ROBERT DANIEL, CHEN, XI STEVEN · 2012 to 2016
$2.3M
Integrative statistical models for TNBC biomarker discoveryR01CA200987 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI CHEN, XI STEVEN · 2016 to 2020
$1.8M
NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA098131NCI NIH HHS R01 CA158472NCI NIH HHS R01 CA200987NCI NIH HHS U24 CA210954
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is a collection of biologically diverse cancers characterized by distinct transcriptional patterns, biology, and immune composition. TNBCs subtypes include two basal-like (BL1, BL2), a mesenchymal (M) and a luminal androgen receptor (LAR) subtype. Through a comprehensive analysis of mutation, copy number, transcriptomic, epigenetic, proteomic, and phospho-proteomic patterns we describe the genomic landscape of TNBC subtypes. Mesenchymal subtype tumors display high mutation loads, genomic instability, absence of immune cells, low PD-L1 expression, decreased global DNA methylation, and transcriptional repression of antigen presentation genes. We demonstrate that major histocompatibility complex I (MHC-I) is transcriptionally suppressed by H3K27me3 modifications by the polycomb repressor complex 2 (PRC2). Pharmacological inhibition of PRC2 subunits EZH2 or EED restores MHC-I expression and enhances chemotherapy efficacy in murine tumor models, providing a rationale for using PRC2 inhibitors in PD-L1 negative mesenchymal tumors. Subtype-specific differences in immune cell composition and differential genetic/pharmacological vulnerabilities suggest additional treatment strategies for TNBC.

Indexed as

AnimalsAntineoplastic AgentsDNA MethylationGene DosageGene Expression ProfilingGene Expression Regulation, NeoplasticGenomicsHistocompatibility Antigens Class IHumansMicePolycomb-Group ProteinsProteogenomicsProteomicsTriple Negative Breast NeoplasmsAntineoplastic AgentsHistocompatibility Antigens Class IPolycomb-Group Proteins

Identifiers

PMID34725325
PMCPMC8560912
OpenAlexW3208558332

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.