Evidence map›Paper›PMID 33618683›Full record

ArticleBMC cancer2021

Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer.

Karoline Berger, Sara Rhost, Svanheiður Rafnsdóttir, Éamon Hughes, Ylva Magnusson, Maria Ekholm, Olle Stål, Lisa Rydén, Göran Landberg

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

Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 25% 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

9 citing papers in PubMed, 14 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

9 authors at 4 institutions in 2 countries.

Karoline BergerDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Box 425, Medicinaregatan 1G, SE-13 90, Gothenburg, Sweden.
Sara RhostDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Box 425, Medicinaregatan 1G, SE-13 90, Gothenburg, Sweden.
Svanheiður RafnsdóttirDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Box 425, Medicinaregatan 1G, SE-13 90, Gothenburg, Sweden.
Éamon HughesDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Box 425, Medicinaregatan 1G, SE-13 90, Gothenburg, Sweden.
Ylva MagnussonDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Box 425, Medicinaregatan 1G, SE-13 90, Gothenburg, Sweden.
Maria EkholmDepartment of Oncology, Region Jönköping County, Jönköping, Sweden.
Olle StålDepartment of Oncology, Region Jönköping County, Jönköping, Sweden.
Lisa RydénDepartment of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden.
Göran LandbergDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Box 425, Medicinaregatan 1G, SE-13 90, Gothenburg, Sweden. goran.landberg@gu.se.
University of Gothenburg · SELinköping University · SELund University · SERegion Jönköpings län · SE

Funding

Cancerfonden 20 0306 PjFCancerfonden 2016-438Cancerfonden 2016-486The Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement 71632The Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement 721091Vetenskapsrådet 2016-01530Vetenskapsrådet 2017-01392
6 · The paper itself

Abstract

backgroundThe growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranulin, via its receptor sortilin, drives breast cancer stem cell propagation in vitro and increases metastasis formation in an in vivo breast cancer xenograft model. In this retrospective biomarker analysis, we aimed to determine whether tumor co-expression of progranulin and sortilin has prognostic and treatment predictive values for breast cancer patients.

methodsWe explored how co-expression of progranulin and sortilin was associated with established clinical markers by analyzing a tissue microarray including 560 randomized premenopausal breast cancer patients receiving either 2 years of tamoxifen treatment or no adjuvant treatment, with a median follow-up time of 28 years. Breast cancer-specific survival was analyzed using Kaplan-Meier and Cox Proportional Hazards regression models to assess the prognostic and predictive value of progranulin and sortilin in relation to known clinical markers.

resultsCo-expression of progranulin and sortilin was observed in 20% of the breast cancer samples. In untreated patients, prognostic considerations could be detailed separately from treatment prediction and the high progranulin and sortilin expressing subgroup was significantly associated with breast cancer-specific death in multivariable analyses (HR=2.188, CI: 1.317-3.637, p=0.003) along with tumor size, high tumor grade and lymph node positivity. When comparing the untreated patients with tamoxifen treated patients in the ERα positive subgroup, co-expression of progranulin and sortilin was not linked to tamoxifen resistance.

conclusionData suggest that co-expression of progranulin and its receptor sortilin is a novel prognostic biomarker combination identifying a highly malignant subgroup of breast cancer. Importantly, this subpopulation could potentially be targeted with anti-sortilin based therapies.

Indexed as

Adaptor Proteins, Vesicular TransportAdultAntineoplastic Agents, HormonalBiomarkers, TumorBreast NeoplasmsFemaleHumansLymphatic MetastasisMiddle AgedNeoplastic Stem CellsPrognosisProgranulinsRandomized Controlled Trials as TopicRetrospective StudiesSortilinSurvival RateAdaptor Proteins, Vesicular TransportAntineoplastic Agents, HormonalBiomarkers, TumorGRN protein, humanProgranulinsSortilinTamoxifenBiomarkerBreast cancerCancer stem cellsEstrogen receptorPredictivePrognosticProgranulinSortilinTamoxifenTargeted therapy

Identifiers

PMID33618683
PMCPMC7898426
OpenAlexW3132889141

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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.