Evidence map›Paper›PMID 30575030›Full record

ArticleThe Journal of pathology2019

Inter- and intra-tumoural heterogeneity in cancer-associated fibroblasts of human pancreatic ductal adenocarcinoma.

Cindy Neuzillet, Annemilaï Tijeras-Raballand, Chanthirika Ragulan, Jérôme Cros, Yatish Patil, Matthieu Martinet, Mert Erkan, Jörg Kleeff, Jeremy Wilson, Minoti Apte and 8 more

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

Article in The Journal of pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
195citing papers in PubMed, 1 pooled it
11.0field-weighted citation impact, top 1% 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

195 citing papers in PubMed, 1 synthesis or guideline pooled it, 278 citations in OpenAlex.

  1. Pooled it
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  11. Modeling CAF-tumor interactions to overcome therapy resistance.Journal of experimental & clinical cancer research : CR · 2026
    Review
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  13. Current Status of Research on Losartan in Tumour Therapy.Journal of cellular and molecular medicine · 2026
    Review
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135 more citing papers are in PubMed but not listed here.

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

18 authors at 7 institutions in 5 countries.

Cindy NeuzilletCentre for Tumour Biology, Barts Cancer Institute - a CRUK Centre of Excellence, Queen Mary University of London, London, UK.ORCID 0000-0001-7037-7477
Annemilaï Tijeras-RaballandAFR Oncology, Paris, France.
Chanthirika RagulanDivision of Molecular Pathology, The Institute of Cancer Research, London, UK.
Jérôme CrosINSERM UMR1149, Beaujon University Hospital, Paris 7 Diderot University, Paris, France.ORCID 0000-0002-4935-3865
Yatish PatilDivision of Molecular Pathology, The Institute of Cancer Research, London, UK.
Matthieu MartinetAFR Oncology, Paris, France.
Mert ErkanDepartment of Surgery, Koc University School of Medicine, Istanbul, Turkey.
Jörg KleeffDepartment of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Jeremy WilsonPancreatic Research Group, South Western Sydney Clinical School, University of New South Wales and Ingham Institute for Applied Medical Research, Sydney, Australia.
Minoti AptePancreatic Research Group, South Western Sydney Clinical School, University of New South Wales and Ingham Institute for Applied Medical Research, Sydney, Australia.
Marie TosoliniINSERM UMR 1037, Technological Pole and Bioinformatic Platform, Cancer Research Center of Toulouse, Toulouse, France.
Abigail S WilsonCentre for Tumour Biology, Barts Cancer Institute - a CRUK Centre of Excellence, Queen Mary University of London, London, UK.
Francesca R DelvecchioCentre for Tumour Biology, Barts Cancer Institute - a CRUK Centre of Excellence, Queen Mary University of London, London, UK.
Corinne BousquetINSERM UMR 1037, Team 6 Protein Synthesis and Secretion in Carcinogenesis, Cancer Research Center of Toulouse, Toulouse, France.
Valérie ParadisINSERM UMR1149, Beaujon University Hospital, Paris 7 Diderot University, Paris, France.
Pascal HammelINSERM UMR1149, Beaujon University Hospital, Paris 7 Diderot University, Paris, France.
Anguraj SadanandamDivision of Molecular Pathology, The Institute of Cancer Research, London, UK.ORCID 0000-0001-8485-5150
Hemant M KocherCentre for Tumour Biology, Barts Cancer Institute - a CRUK Centre of Excellence, Queen Mary University of London, London, UK.ORCID 0000-0001-6771-1905
Inserm · FRQueen Mary University of London · GBRoyal Marsden NHS Foundation Trust · GBAssociation Française de Lutte Anti-Rhumastismale · FRUNSW Sydney · AUKoç University · TRMartin Luther University Halle-Wittenberg · DE

Funding

Cancer Research UK C16420/A18066
6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAF) are orchestrators of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Stromal heterogeneity may explain differential pathophysiological roles of the stroma (pro- versus anti-tumoural) in PDAC. We hypothesised that multiple CAF functional subtypes exist in PDAC, that contribute to stromal heterogeneity through interactions with cancer cells. Using molecular and functional analysis of patient-derived CAF primary cultures, we demonstrated that human PDAC-derived CAFs display a high level of inter- and intra-tumour heterogeneity. We identified at least four subtypes of CAFs based on transcriptomic analysis, and propose a classification for human PDAC-derived CAFs (pCAFassigner). Multiple CAF subtypes co-existed in individual patient samples. The presence of these CAF subtypes in bulk tumours was confirmed using publicly available gene expression profiles, and immunostainings of CAF subtype markers. Each subtype displayed specific phenotypic features (matrix- and immune-related signatures, vimentin and α-smooth muscle actin expression, proliferation rate), and was associated with an assessable prognostic impact. A prolonged exposure of non-tumoural pancreatic stellate cells to conditioned media from cancer cell lines (cancer education experiment) induced a CAF-like phenotype, including loss of capacity to revert to quiescence and an increase in the expression of genes related to CAF subtypes B and C. This classification demonstrates molecular and functional inter- and intra-tumoural heterogeneity of CAFs in human PDAC. Our subtypes overlap with those identified from single-cell analyses in other cancers, and pave the way for the development of therapies targeting specific CAF subpopulations in PDAC. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Indexed as

Cancer-Associated FibroblastsCarcinoma, Pancreatic DuctalGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic HeterogeneityHumansKaplan-Meier EstimatePancreatic NeoplasmsPancreatic Stellate CellsPhenotypePrognosisStromal CellsTumor Cells, CulturedTumor Microenvironmentpancreatic stellate cellstromatranscriptomicstumour microenvironmenttumour-stroma interactions

Identifiers

PMID30575030
PMCPMC6492001
OpenAlexW2905888775

What OpenQuestion holds

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LicenceCC BY
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 OpenQuestion graph.