Evidence map›Paper›PMID 30922247›Full record

ArticleBMC cancer2019

Increased expression of cancer-associated fibroblast markers at the invasive front and its association with tumor-stroma ratio in colorectal cancer.

Tessa P Sandberg, Maaike P M E Stuart, Jan Oosting, Rob A E M Tollenaar, Cornelis F M Sier, Wilma E Mesker

Open access · goldAbstract readComparative Study
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
8.2field-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

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.

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  14. Comparison of the diagnostic accuracy betweenJournal of thoracic disease · 2025
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25 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

6 authors at 1 institution in 1 country.

Tessa P SandbergDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands. t.p.sandberg@lumc.nl.ORCID http://orcid.org/0000-0001-5037-798X
Maaike P M E StuartDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands.
Jan OostingDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands.
Rob A E M TollenaarDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands.
Cornelis F M SierDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands.
Wilma E MeskerDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands.
Leiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe tumor microenvironment has a critical role in regulating cancer cell behavior. Tumors with high stromal content are associated with poor patient outcome. The tumor-stroma ratio (TSR) identifies colorectal cancers (CRC) with poor patient prognosis based on hematoxylin & eosin stained sections. The desmoplastic reaction consists to a great extent of cancer-associated fibroblasts (CAFs) of which different subtypes are known. The aim of this study is to investigate and quantify CAFs present in the tumor stroma of CRC stratified by the TSR to possibly add prognostic significance to the TSR.

methodsThe expression of established CAF markers was compared between stroma-low and stroma-high tumors using transcriptomic data of 71 stage I - III CRC. Based on literature, fibroblast and stromal markers were selected to perform multiplex immunofluorescent staining on formalin fixed, paraffin-embedded tumor sections of patients diagnosed with stage III colon cancer. Antibodies against the following markers were used: αSMA, PDGFR -β, FAP, FSP1 and the stromal markers CD45 and CD31 as reference. The markers were subsequently quantified in the stroma using the Vectra imaging microscope.

resultsThe transcriptomic data showed that all CAF markers except one were higher expressed in stroma-high compared to stroma-low tumors. Histologically, stroma-high tumors showed a decreased number of FSP1

conclusionsThe increased expression of FAP at the invasive part and in stroma-high tumors might contribute to the invasive behavior of cancer cells. Future functional experiments should investigate the contribution of FAP to cancer cell invasion. Combining the quantity of the stroma as defined by the TSR with the activity level of CAFs using the expression of FAP may result in an expanded stroma-based tool for patient stratification.

Indexed as

Up-RegulationBiomarkers, TumorCancer-Associated FibroblastsCell Line, TumorColorectal NeoplasmsEndopeptidasesFibroblast Activation Protein AlphaGelatinasesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMembrane ProteinsNeoplasm InvasivenessNeoplasm StagingOligonucleotide Array Sequence AnalysisPrognosisBiomarkers, TumorEndopeptidasesFibroblast Activation Protein AlphaGelatinasesMembrane ProteinsSerine EndopeptidasesCancer-associated fibroblastsColorectal cancerFAPTumor microenvironmentTumor-stroma ratio

Identifiers

PMID30922247
PMCPMC6440123
OpenAlexW2947857926

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Textmetadata
LicenceCC BY
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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.