Evidence map›Paper›PMID 40499545›Full record

ArticleCell reports. Medicine2025

Cell states and neighborhoods in distinct clinical stages of primary and metastatic esophageal adenocarcinoma.

Josephine Yates, Camille Mathey-Andrews, Jihye Park, Amanda Garza, Andréanne Gagné, Samantha Hoffman, Kevin Bi, Breanna Titchen, Connor Hennessey, Joshua Remland and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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  7. Review
  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Josephine YatesInstitute for Machine Learning, Department of Computer Science, ETH Zürich, Zurich, Switzerland; ETH AI Center, ETH Zurich, Zurich, Switzerland; Swiss Institute for Bioinformatics (SIB), Lausanne, Switzerland; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Camille Mathey-AndrewsDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Jihye ParkDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Amanda GarzaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Andréanne GagnéDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Samantha HoffmanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Medical Sciences, Harvard University, Boston, MA, USA.
Kevin BiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Breanna TitchenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Medical Sciences, Harvard University, Boston, MA, USA.
Connor HennesseyPenn Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Joshua RemlandDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Matthew CarnesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Erin ShannonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sabrina CampDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Siddhi BalamuraliDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Shweta Kiran CavaleDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Zhixin LiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Akhouri Kishore RaghawanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Agnieszka KraftInstitute for Machine Learning, Department of Computer Science, ETH Zürich, Zurich, Switzerland; Swiss Institute for Bioinformatics (SIB), Lausanne, Switzerland.
Genevieve BolandDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Andrew J AguirreDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Medical Sciences, Harvard University, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nilay S SethiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Valentina BoevaInstitute for Machine Learning, Department of Computer Science, ETH Zürich, Zurich, Switzerland; ETH AI Center, ETH Zurich, Zurich, Switzerland; Swiss Institute for Bioinformatics (SIB), Lausanne, Switzerland; Cochin Institute, Inserm U1016, CNRS UMR 8104 Paris Descartes University UMR-S1016, Paris 75014, France. Electronic address: valentina.boeva@inf.ethz.ch.
Eliezer M Van AllenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Medical Sciences, Harvard University, Boston, MA, USA; Parker Institute for Cancer Immunotherapy, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: eliezerm_vanallen@dfci.harvard.edu.

Funding

Mechanisms of response and resistance to KRAS inhibition in pancreatic cancerR01CA276268 · NCI · DANA-FARBER CANCER INST · PI Andrew James Aguirre · 2023 to 2026
$2.2M
Molecular origins and evolution to treatment resistance in genitourinary cancersR50CA265182 · NCI · DANA-FARBER CANCER INST · PI Jihye Park · 2022 to 2026
$1.7M
NCI NIH HHS R01 CA276268NCI NIH HHS R50 CA265182
6 · The paper itself

Abstract

Esophageal adenocarcinoma (EAC) is a highly lethal cancer of the upper gastrointestinal tract with rising incidence in western populations. To decipher EAC disease progression and therapeutic response, we perform multiomic analyses of a cohort of primary and metastatic EAC tumors, incorporating single-nuclei transcriptomic and chromatin accessibility sequencing along with spatial profiling. We recover tumor microenvironmental features previously described to associate with therapy response. We subsequently identify five malignant cell programs, including undifferentiated, intermediate, differentiated, epithelial-to-mesenchymal transition, and cycling programs, which are associated with differential epigenetic plasticity and clinical outcomes, and for which we infer candidate transcription factor regulons. Furthermore, we reveal diverse spatial localizations of malignant cells expressing their associated transcriptional programs and predict their significant interactions with microenvironmental cell types. We validate our findings in three external single-cell RNA sequencing (RNA-seq) and three bulk RNA-seq studies. Altogether, our findings advance the understanding of EAC heterogeneity, disease progression, and therapeutic response.

Indexed as

AdenocarcinomaEsophageal NeoplasmsDisease ProgressionEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansMaleNeoplasm MetastasisNeoplasm StagingTranscriptomeTumor Microenvironmentbioinformaticscomputational biologyepigeneticsesophageal adenocarcinomagastrointestinal canceroncologysingle cellspatial transcriptomicstranscriptomics

Identifiers

PMID40499545
PMCPMC12208317

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 Socratic graph.