Evidence map›Paper›PMID 41319863›Full record

ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2026

Multiomic, Histologic, and scRNA-seq Profiling of Pleural Mesothelioma Reveals Negative Prognosis Associated With a Novel Uncommitted Molecular Phenotype.

David T Severson, Samuel Freyaldenhoven, Benjamin Wadowski, Yin P Hung, Travis Hughes, Beow Y Yeap, William G Richards, Sanna Laaksonen, Lucian Chirieac, Matthew B Couger and 14 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

David T SeversonThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts; Duke University Health System, Durham, North Carolina.
Samuel FreyaldenhovenThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Benjamin WadowskiThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Yin P HungDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Travis HughesRagon Institute of MGH, Harvard, and MIT, Cambridge, Massachusetts; Department of Chemistry, Institute for Medical Engineering and Sciences (IMES) and Koch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Beow Y YeapDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
William G RichardsThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Sanna LaaksonenDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Lucian ChirieacDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Matthew B CougerThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Roderick V JensenThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Ahmed A SadekThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Ilkka IlonenThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Kimberly VermilyaThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Simona InnocentiThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Stephanie L KorleThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Julianne S BarlowThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Jamie AndersonThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Jason MeyerovitzThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Vivian WangThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Mary N DaoThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Alex K ShalekRagon Institute of MGH, Harvard, and MIT, Cambridge, Massachusetts; Department of Chemistry, Institute for Medical Engineering and Sciences (IMES) and Koch Institute for Integrative Cancer Research, MIT, Cambridge, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Assunta De RienzoThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
Raphael BuenoThe Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts. Electronic address: rbueno@bwh.harvard.edu.

Funding

Validation of Prognostic and Diagnostic Molecular Tests in MesotheliomaR01CA120528 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BUENO, RAPHAEL · 2006 to 2021
$4.8M
NCI NIH HHS R01 CA120528Wellcome Trust
6 · The paper itself

Abstract

introductionMultiomics pleural mesothelioma (PM) studies have identified prognostic molecular subsets of PM histologic types, epithelioid (ePM), biphasic (bPM), and sarcomatoid (sPM), defined by relative tumor cell content. However, the underlying biology modulating survival remains unknown.

methodsUsing 93 samples from 40 patients, we performed single-cell RNA sequencing (scRNA-seq), bulk exome and RNA sequencing, optical genome mapping, spatial transcriptomics, and histologic analyses to identify candidate drivers and prognostic biomarkers of malignant cell (MC) state.

resultsWe identified a novel uncommitted MC state enriched in bPM tumors. Using inferred copy number variants, we observed all three MC states within individual clones suggesting MC state is not clonally restricted. We identified TGF-β and GAS6-AXL signaling as candidate MC state drivers for further study. Finally, we validated two prognostic MC state immunohistochemistry biomarkers, MEST (uncommitted) and MSLN (epithelioid).

conclusionsThese multiomic, scRNA-seq analyses of primary patient tissues provide new candidate drivers of MC state and novel biomarkers to improve patient stratification. Further experimental exploration and clinical validation of these findings may reveal new treatment strategies and refine current clinical decision-making in PM.

Indexed as

Biomarkers, TumorLung NeoplasmsMesotheliomaPleural NeoplasmsAgedFemaleHumansMaleMesothelioma, MalignantMiddle AgedPhenotypePrognosisRNA-SeqSingle-Cell AnalysisSingle-Cell Gene Expression AnalysisBiomarkers, TumorCancer cell heterogeneityMesothelioma prognosisPleural mesotheliomaSingle cell RNA-seqSpatial transcriptomicsTumor micro-environment

Identifiers

PMID41319863
PMCPMC12853269

What OpenQuestion holds

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Registered trials

None linked

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.