Evidence map›Paper›PMID 40029262›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025

Single-Cell RNA Sequencing of Ewing Sarcoma Tumors Demonstrates Transcriptional Heterogeneity and Clonal Evolution.

Andrew Goodspeed, Avery Bodlak, Alexis B Duffy, Sarah Nelson-Taylor, Naoki Oike, Timothy Porfilio, Ryota Shirai, Deandra Walker, Amanda Treece, Jennifer Black and 11 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. 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

21 authors.

Andrew GoodspeedUniversity of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0001-7055-7128
Avery BodlakDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0001-9207-1532
Alexis B DuffyCreatv MicroTech, Monmouth Junction, New Jersey.ORCID 0009-0009-6051-5552
Sarah Nelson-TaylorDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0009-0003-7664-4400
Naoki OikeDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0003-3067-392X
Timothy PorfilioDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0003-3699-9963
Ryota ShiraiDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0002-1015-3444
Deandra WalkerDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0009-0003-7619-1616
Amanda TreeceDepartment of Pathology and Laboratory Medicine, Children's of Alabama, Birmingham, Alabama.ORCID 0000-0002-6083-7166
Jennifer BlackDepartment of Pathology and Laboratory Medicine, Children's of Alabama, Birmingham, Alabama.ORCID 0000-0002-2181-9344
Nathan DonaldsonDepartment of Orthopedics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0001-6595-804X
Carrye CostDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0009-0005-1780-9097
Timothy GarringtonDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0002-8843-8343
Brian GreffeDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0009-0005-8569-6741
Sandra Luna-FinemanDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0003-0713-7651
Jenna DemedisDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0001-5191-7511
Jessica LakeDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0001-7739-0850
Etienne DanisUniversity of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0002-5651-8111
Michael R VernerisDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0002-7097-5917
Daniel L AdamsCreatv MicroTech, Monmouth Junction, New Jersey.ORCID 0000-0002-1916-9637
Masanori HayashiUniversity of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0002-9508-0159

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Training in Basic and Translational Child Health ResearchK12HD068372 · NICHD · UNIVERSITY OF COLORADO DENVER · PI DANIELS, STEPHEN R · 2011 to 2020
$3.7M
Cancer Research Education And Training ExperienceR25CA200508 · NCI · UNIVERSITY OF MINNESOTA · PI SCHWERTFEGER, KATHRYN L, SHIMIZU, YOJI · 2015 to 2025
$1.5M
Congressionally Directed Medical Research Programs (CDMRP) CA200508Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) K12HD068372Hyundai Hope On Wheels (Hope On Wheels) Young Investigator AwardNational Cancer Institute (NCI) P30CA046934National Science Foundation (NSF) 2201538NCI NIH HHS P30 CA046934NCI NIH HHS R25 CA200508NICHD NIH HHS K12 HD068372
6 · The paper itself

Abstract

purposeEwing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis compared with the >70% 5-year survival of those with localized disease. Novel therapeutic approaches that can impact metastatic disease are desperately needed, as well as a deeper understanding of the heterogeneity of Ewing sarcoma tumors. EXPERIMENTAL

designIn this study, we utilized single-cell RNA sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and the surrounding tumor microenvironment in a cohort of seven untreated patients with Ewing sarcoma, as well as in circulating tumor cells (CTC). A potential CTC therapeutic target was evaluated through immunofluorescence of fixed CTCs from a separate cohort.

resultsPrimary tumor samples demonstrate a heterogeneous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and Ewing sarcoma gene targets, which were found to correlate with overall survival. Copy-number analysis identified subclonal evolution within patients prior to treatment. Analyses of the immune microenvironment reveal an immunosuppressive microenvironment with complex intercellular communication among the tumor and immune cells. Single-cell RNA sequencing and immunofluorescence of CTCs at the time of diagnosis identified TSPAN8 as a potential therapeutic target.

conclusionsEwing sarcoma tumors demonstrate significant transcriptional heterogeneity as well as a complex immunosuppressive microenvironment. This work evaluates several proposed targets that warrant further exploration as novel therapeutic strategies.

Indexed as

Biomarkers, TumorBone NeoplasmsClonal EvolutionGenetic HeterogeneitySarcoma, EwingSingle-Cell AnalysisAdolescentChildFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleNeoplastic Cells, CirculatingPrognosisSequence Analysis, RNABiomarkers, Tumor

Identifiers

PMID40029262
PMCPMC12081191

What Socratic 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 Socratic graph.