Evidence map›Paper›PMID 33955203›Full record

ArticleThe journal of pathology. Clinical research2021

High tumor cell platelet-derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma.

Hely Ollila, Juuso Paajanen, Henrik Wolff, Ilkka Ilonen, Eva Sutinen, Katja Välimäki, Arne Östman, Sisko Anttila, Eeva Kettunen, Jari Räsänen and 4 more

Open access · goldAbstract read
In one paragraph

Article in The journal of pathology. Clinical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

8 citing papers in PubMed, 11 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

14 authors at 3 institutions in 2 countries.

Hely OllilaInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.ORCID 0000-0001-5381-4188
Juuso PaajanenIndividualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Henrik WolffLaboratory of Pathology, Finnish Institute of Occupational Health, Helsinki, Finland.
Ilkka IlonenIndividualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Eva SutinenIndividualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Katja VälimäkiInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Arne ÖstmanDepartment of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.ORCID 0000-0002-8799-4874
Sisko AnttilaDepartment of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Eeva KettunenLaboratory of Pathology, Finnish Institute of Occupational Health, Helsinki, Finland.
Jari RäsänenDepartment of General Thoracic and Esophageal Surgery, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Olli KallioniemiInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Marjukka MyllärniemiIndividualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Mikko I MäyränpääDepartment of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Teijo PellinenInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.ORCID 0000-0001-9652-7373
University of Helsinki · FIFinnish Institute of Occupational Health · FIKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location-specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all-cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet-derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p < 0.001). A multivariable survival analysis adjusted for clinical parameters and stromal mfIHC markers revealed that tumor cell PDGFRB and stromal SPARC remained independently associated with survival (HR = 1.01, 95% confidence interval [CI] = 1.00-1.03 and HR = 1.05, 95% CI = 1.00-1.11, respectively). The prognostic effect of PDGFRB was validated with an artificial intelligence-based analysis method and further externally validated in another cohort of 117 MPM patients. In external validation, high tumor cell PDGFRB expression associated with shorter survival, especially in the epithelioid subtype. Our findings suggest PDGFRB and SPARC as potential markers for risk stratification and as targets for therapy.

Indexed as

AgedArtificial IntelligenceBiomarkers, TumorCohort StudiesFemaleFibroblastsHumansImage Processing, Computer-AssistedImmunohistochemistryMaleMesothelioma, MalignantOsteonectinPleural NeoplasmsPrognosisReceptor, Platelet-Derived Growth Factor betaSurvival AnalysisBiomarkers, TumorOsteonectinReceptor, Platelet-Derived Growth Factor betaSPARC protein, humanfibroblastmesotheliomaplatelet-derived growth factor receptor betaprognosis

Identifiers

PMID33955203
PMCPMC8363931
OpenAlexW3159692505

What OpenQuestion holds

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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.