Evidence map›Paper›PMID 41543983›Full record

ArticlePathobiology : journal of immunopathology, molecular and cellular biology2026

Tissue-Based Multiomic Exploratory Analysis of the Urokinase Plasminogen Activator/uPAR System and Matrix Metalloproteinases in Stroma AReactive Invasion Front Areas-Positive Gastrointestinal Cancers.

Nic G Reitsam, Bianca Grosser, Sebastian Dintner, Veselin Grozdanov, Florian Sommer, Christian Heyer, Matthias Schlesner, Jochen Hardt, Simon Franz, Gerhard Schenkirsch and 4 more

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In one paragraph

Article in Pathobiology : journal of immunopathology, molecular and cellular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

14 authors.

Nic G ReitsamPathology, Faculty of Medicine, University of Augsburg, Augsburg, Germany, nic.reitsam@uka-science.de.
Bianca GrosserPathology, Faculty of Medicine, University of Augsburg, Augsburg, Germany, bianca.grosser@uka-science.de.
Sebastian DintnerPathology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
Veselin GrozdanovDepartment of Neurology, Ulm University, Ulm, Germany.
Florian SommerGeneral and Visceral Surgery, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
Christian HeyerBiomedical Informatics, Data Mining and Data Analytics, Faculty of Applied Computer Science and Medical Faculty, University of Augsburg, Augsburg, Germany.
Matthias SchlesnerBiomedical Informatics, Data Mining and Data Analytics, Faculty of Applied Computer Science and Medical Faculty, University of Augsburg, Augsburg, Germany.
Jochen HardtInstitute of Laboratory Medicine and Microbiology, University Hospital Augsburg, Augsburg, Germany.
Simon FranzDepartment of General, Abdominal and Thoracic Surgery, German Armed Forces Hospital Ulm, Ulm, Germany.
Gerhard SchenkirschTumour Data Management, University Hospital Augsburg, Augsburg, Germany.
Andreas ProbstGastroenterology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
Phillip LöhrHematology and Oncology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
Johanna WaidhauserBavarian Cancer Research Center (BZKF), Augsburg, Germany.
Bruno MärklPathology, Faculty of Medicine, University of Augsburg, Augsburg, Germany, bruno.maerkl@uka-science.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

<p>Introduction: We recently proposed SARIFA (Stroma AReactive Invasion Front Areas), defined as direct tumour-adipocyte interaction, as an H&E-based histopathologic biomarker in gastrointestinal cancers, particularly gastric cancer (GC) and colorectal cancer (CRC). Despite SARIFA's well-validated prognostic value, its mechanistic underpinnings remain unclear. We hypothesized that extracellular matrix remodelling, specifically the plasmin/plasminogen activator system, may contribute to SARIFA formation.

methodsTo test this, we compared the prognostic value of H&E-based SARIFA status with enzyme-linked immunosorbent assay (ELISA)-based protein levels of the serine proteases urokinase-type plasminogen activator (uPA, encoded by PLAU) and plasminogen activator inhibitor-1 (PAI-1, encoded by SERPINE1) in CRC. We further examined associations between SARIFA status and the plasmin/plasminogen activator system as well as downstream metalloproteinases using both protein (ELISA, immunohistochemistry) and bulk gene expression data (TCGA-COAD/READ and TCGA-STAD), as well as spatial gene expression profiling in CRC (n = 8) and GC (n = 12).

resultsOur findings show that high expression of the plasmin/plasminogen activator system and downstream metalloproteinases correlates with SARIFA positivity. Digital spatial profiling revealed PLAU upregulation in tumour cells and PLAUR (encoding uPAR) upregulation in adjacent stromal cells at SARIFAs, suggesting a potential receptor-ligand interaction. Notably, SARIFA-positive tumours showed significantly higher numbers of tumour buds.

conclusionThese results provide new insights into the biological basis of SARIFAs and suggest therapeutic vulnerabilities related to the plasmin/plasminogen activator system. </p>.

Indexed as

Colorectal NeoplasmsGastrointestinal NeoplasmsMatrix MetalloproteinasesReceptors, Urokinase Plasminogen ActivatorUrokinase-Type Plasminogen ActivatorBiomarkers, TumorEnzyme-Linked Immunosorbent AssayFemaleFibrinolysinGene Expression ProfilingHumansMaleMembrane ProteinsMultiomicsNeoplasm InvasivenessPlasminogen Activator Inhibitor 1Biomarkers, TumorFibrinolysinMatrix MetalloproteinasesMembrane ProteinsPlasminogen Activator Inhibitor 1PLAU protein, humanReceptors, Urokinase Plasminogen ActivatorSERPINE1 protein, humanUrokinase-Type Plasminogen ActivatorCancerColon cancerGastrointestinal cancerGene expression profilingLipid metabolismPathologySurgical pathology

Identifiers

PMID41543983
PMCPMC12935455

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.