Evidence map›Paper›PMID 30358171›Full record

ArticleThe journal of pathology. Clinical research2019

Combined epithelial marker analysis of tumour budding in stage II colorectal cancer.

Khadija Slik, Sami Blom, Riku Turkki, Katja Välimäki, Samu Kurki, Harri Mustonen, Caj Haglund, Olli Carpén, Olli Kallioniemi, Eija Korkeila and 2 more

Open access · goldAbstract read
In one paragraph

Article in The journal of pathology. Clinical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.2field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

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  9. Oxymatrine reduces expression of programmed death-ligand 1 by promoting DNA demethylation in colorectal cancer cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
    Article
  10. Tumour budding in solid cancers.Nature reviews. Clinical oncology · 2021
    Review
  11. Prognostic impact of tumor budding in endometrial carcinoma within distinct molecular subgroups.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021
    Article
  12. Roles of Integrins in Gastrointestinal Cancer Metastasis.Frontiers in molecular biosciences · 2021
    Review
  13. Article
  14. Article
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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

12 authors at 6 institutions in 3 countries.

Khadija SlikDepartment of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
Sami BlomInstitute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
Riku TurkkiInstitute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
Katja VälimäkiInstitute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
Samu KurkiAuria Biobank, University of Turku and Turku University Hospital, Turku, Finland.
Harri MustonenDepartment of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Caj HaglundDepartment of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Olli CarpénDepartment of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
Olli KallioniemiInstitute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
Eija KorkeilaDepartment of Oncology, Turku University Hospital, Hämeentie 11, Turku, Finland.
Jari SundströmDepartment of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
Teijo PellinenInstitute for Molecular Medicine Finland (FIMM), Helsinki, Finland.ORCID 0000-0001-9652-7373
Institute for Molecular Medicine Finland · FIUniversity of Helsinki · FIUniversity of Turku · FIMisurata University · LYScience for Life Laboratory · SETurku University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumour budding predicts survival of stage II colorectal cancer (CRC) and has been suggested to be associated with epithelial-to-mesenchymal transition (EMT). However, the underlying molecular changes of tumour budding remain poorly understood. Here, we performed multiplex immunohistochemistry (mIHC) to phenotypically profile tumours using known EMT-associated markers: E-cadherin (adherence junctions), integrin β4 (ITGB4; basement membrane), ZO-1 (tight junctions), and pan-cytokeratin. A subpopulation of patients showed high ITGB4 expression in tumour buds, and this coincided with a switch of ITGB4 localisation from the basal membrane of intact epithelium to the cytoplasm of budding cells. Digital image analysis demonstrated that tumour budding with high ITGB4 expression in tissue microarray (TMA) cores correlated with tumour budding assessed from haematoxylin and eosin (H&E) whole sections and independently predicted poor disease-specific survival in two independent stage II CRC cohorts (hazard ratio [HR] = 4.50 (95% confidence interval [CI] = 1.50-13.5), n = 232; HR = 3.52 (95% CI = 1.30-9.53), n = 72). Furthermore, digitally obtained ITGB4-high bud count in random TMA cores was better associated with survival outcome than visual tumour bud count in corresponding H&E-stained samples. In summary, the mIHC-based phenotypic profiling of human tumour tissue shows strong potential for the molecular characterisation of tumour biology and for the discovery of novel prognostic biomarkers.

Indexed as

AdultAgedAged, 80 and overAntigens, CDBiomarkers, TumorCadherinsColorectal NeoplasmsEpithelial-Mesenchymal TransitionFemaleHumansIntegrin beta4KeratinsMaleMiddle AgedNeoplasm StagingPrognosisAntigens, CDBiomarkers, TumorCadherinsCDH1 protein, humanIntegrin beta4ITGB4 protein, humanKeratinscolorectal cancerdigital pathologyepithelial-to-mesenchymal transitionintegrin β4multiplex immunohistochemistryprognosticstumour budding

Identifiers

PMID30358171
PMCPMC6317060
OpenAlexW2898258250

What OpenQuestion holds

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LicenceCC BY-NC
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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.