Evidence map›Paper›PMID 33148332›Full record

ArticleGenome biology2020

Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity.

Won-Chul Lee, Alexandre Reuben, Xin Hu, Nicholas McGranahan, Runzhe Chen, Ali Jalali, Marcelo V Negrao, Shawna M Hubert, Chad Tang, Chia-Chin Wu and 36 more

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

Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.6field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 62 citations in OpenAlex.

  1. Ionizing Radiation Enhances Prognostically Significant Cellular Immunity Programs in the Brain Metastasis Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  10. Genomic Staging of Multifocal Lung Squamous Cell Carcinomas Is Independent of the Comprehensive Morphologic Assessment.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024
    Article
  11. Molecular features of NSCLC patients with liver metastasis.Therapeutic advances in medical oncology · 2024
    Article
  12. Pathomic Features Reveal Immune and Molecular Evolution From Lung Preneoplasia to Invasive Adenocarcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2023
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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

46 authors at 9 institutions in 3 countries.

Won-Chul LeeDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alexandre ReubenDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. areuben@mdanderson.org.
Xin HuDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nicholas McGranahanCancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Runzhe ChenDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ali JalaliDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
Marcelo V NegraoDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shawna M HubertDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chad TangDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chia-Chin WuDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anthony San LucasDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Whijae RohBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Kenichi SudaDepartment of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Jihye KimDivision of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Aik-Choon TanDepartment of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA.
David H PengNYU Langone Health, New York, NY, USA.
Wei LuDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ximing TangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chi-Wan ChowDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Junya FujimotoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Carmen BehrensDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Neda KalhorDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kazutaka FukumuraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Marcus CoyleDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rebecca ThorntonDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Curtis GumbsDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jun LiDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chang-Jiun WuDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Latasha LittleDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Emily RoartyDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xingzhi SongDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Jack LeeDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Erik P SulmanNew York University Langone School of Medicine, New York, NY, USA.
Ganesh RaoDepartment of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Stephen SwisherDepartment of Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lixia DiaoDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jing WangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
John V HeymachDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jason T HuseDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Paul ScheetDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ignacio I WistubaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Don L GibbonsDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
P Andrew FutrealDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jianhua ZhangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Daniel GomezDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. danielrgomez44@gmail.com.
Jianjun ZhangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. jzhang20@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USNYU Langone Health · USBaylor College of Medicine · USBroad Institute · USCancer Research UK · GBKindai University · JPMemorial Sloan Kettering Cancer Center · USMoffitt Cancer Center · USUniversity of Colorado Anschutz Medical Campus · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Cancer Research UK 24956NCI NIH HHS P30 CA016672Wellcome Trust 211179/Z/18/Z
6 · The paper itself

Abstract

backgroundMetastasis is the primary cause of cancer mortality accounting for 90% of cancer deaths. Our understanding of the molecular mechanisms driving metastasis is rudimentary.

resultsWe perform whole exome sequencing (WES), RNA sequencing, methylation microarray, and immunohistochemistry (IHC) on 8 pairs of non-small cell lung cancer (NSCLC) primary tumors and matched distant metastases. Furthermore, we analyze published WES data from 35 primary NSCLC and metastasis pairs, and transcriptomic data from 4 autopsy cases with metastatic NSCLC and one metastatic lung cancer mouse model. The majority of somatic mutations are shared between primary tumors and paired distant metastases although mutational signatures suggest different mutagenesis processes in play before and after metastatic spread. Subclonal analysis reveals evidence of monoclonal seeding in 41 of 42 patients. Pathway analysis of transcriptomic data reveals that downregulated pathways in metastases are mainly immune-related. Further deconvolution analysis reveals significantly lower infiltration of various immune cell types in metastases with the exception of CD4+ T cells and M2 macrophages. These results are in line with lower densities of immune cells and higher CD4/CD8 ratios in metastases shown by IHC. Analysis of transcriptomic data from autopsy cases and animal models confirms that immunosuppression is also present in extracranial metastases. Significantly higher somatic copy number aberration and allelic imbalance burdens are identified in metastases.

conclusionsMetastasis is a molecularly late event, and immunosuppression driven by different molecular events, including somatic copy number aberration, may be a common characteristic of tumors with metastatic plasticity.

Indexed as

Immunosuppression TherapyAnimalsCarcinoma, Non-Small-Cell LungDisease Models, AnimalDNA MethylationExome SequencingGene Expression Regulation, NeoplasticGenomicsHumansImmunohistochemistryLung NeoplasmsMiceMutationNeoplasm MetastasisTranscriptomeDNA methylationGene expressionGenomicsImmune profilingLung cancerMetastasisMultiomics

Identifiers

PMID33148332
PMCPMC7640699
OpenAlexW3097803023

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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.