Evidence map›Paper›PMID 37857854›Full record

ArticleNPJ precision oncology2023

High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival.

Erik P Storrs, Prathamesh Chati, Abul Usmani, Ian Sloan, Bradley A Krasnick, Ramandeep Babbra, Peter K Harris, Chloe M Sachs, Faridi Qaium, Deyali Chatterjee and 20 more

Open access · goldAbstract read
In one paragraph

Article in NPJ precision oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
8.1field-weighted citation impact, top 2% 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

36 citing papers in PubMed, 35 citations in OpenAlex.

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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

30 authors at 5 institutions in 1 country.

Erik P Storrs *Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Prathamesh Chati *Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Abul Usmani *Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-5485-7323
Ian SloanDivision of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Bradley A KrasnickDepartment of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Ramandeep BabbraDivision of Hematology & Oncology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Peter K HarrisDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Chloe M SachsDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Faridi QaiumDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Deyali ChatterjeeDivision of Laboratory Medicine, Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA.
Chris WetzelDepartment of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
S Peter GoedegebuureDepartment of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Thomas HollanderDivision of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Hephzibah AnthonyDivision of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Jennifer PonceMcDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
Ateeq M KhaliqDivision of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0001-5200-081X
Shahed BadiyanDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Hyun KimDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
David G DenardoSiteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
Gabriel D LangDivision of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Natalie D CosgroveDivision of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Vladimir M KushnirDivision of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Dayna S EarlyDivision of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Ashiq MasoodDivision of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Kian-Huat LimSiteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-2766-200X
William G HawkinsDepartment of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Li DingDepartment of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Ryan C FieldsDivision of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-6176-8943
Koushik K DasDivision of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. k.das@wustl.edu.
Aadel A ChaudhuriDepartment of Genetics, Washington University School of Medicine, St. Louis, MO, USA. aadel@wustl.edu.ORCID http://orcid.org/0000-0003-3115-3061
Washington University in St. Louis · USIndiana University School of MedicineJames S. McDonnell Foundation · USThe University of Texas MD Anderson Cancer Center · USUniversity of Rochester Medical Center · US

Funding

Washington University Participant Engagement and Cancer Genomic Sequencing Center (WU-PE-CGS)U2CCA252981 · NCI · WASHINGTON UNIVERSITY · PI GRAHAM A. COLDITZ, Li Ding · 2021 to 2026
$18.5M
Washington University SPORE in Pancreatic CancerP50CA196510 · NCI · WASHINGTON UNIVERSITY · PI WANG-GILLAM, ANDREA · 2016 to 2020
$10.9M
Washington University SPORE in Pancreatic CancerP50CA272213 · NCI · WASHINGTON UNIVERSITY · PI David G DeNardo, WILLIAM G HAWKINS · 2023 to 2026
$10.7M
WASHINGTON UNIVERSITY HUMAN TUMOR ATLAS RESEARCH CENTERU2CCA233303 · NCI · WASHINGTON UNIVERSITY · PI DING, LI · 2018 to 2023
$9.7M
Cell-Free Nucleic Acids for Early Treatment Response Assessment of Hepatocellular CancerK08CA238711 · NCI · WASHINGTON UNIVERSITY · PI CHAUDHURI, AADEL · 2019 to 2021
$647k
NCI NIH HHS K08 CA238711NCI NIH HHS P50 CA196510NCI NIH HHS P50 CA272213NCI NIH HHS U2C CA233303NCI NIH HHS U2C CA252981
6 · The paper itself

Abstract

Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n = 25). We then combined these samples with surgical resection (n = 6) and publicly available samples to increase statistical power (n = 80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness, and a customized version of the Ecotyper tool was used to identify communities of co-occurring cell states in bulk RNA-seq samples (n = 268). We discovered a tumor microenvironmental community comprised of aggressive basal-like malignant cells, tumor-promoting SPP1+ macrophages, and myofibroblastic cancer-associated fibroblasts associated with especially poor prognosis. We also found a developmental stemness continuum with implications for survival that is present in both malignant cells and cancer-associated fibroblasts (CAFs). We further demonstrated that high-dimensional analyses predictive of survival are feasible using standard-of-care, time-of-diagnosis EUS-FNB specimens. In summary, we identified tumor microenvironmental and developmental stemness characteristics from a high-dimensional gene expression analysis of PDAC using human tissue specimens, including time-of-diagnosis EUS-FNB samples. These reveal new connections between tumor microenvironmental composition, CAF and malignant cell stemness, and patient survival that could lead to better upfront risk stratification and more personalized upfront clinical decision-making.

Identifiers

PMID37857854
PMCPMC10587349
OpenAlexW4387779197

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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.