Evidence map›Paper›PMID 30987640›Full record

ArticleJournal of translational medicine2019

RSPO3 is a prognostic biomarker and mediator of invasiveness in prostate cancer.

Aruz Mesci, Fabrice Lucien, Xiaoyong Huang, Eric H Wang, David Shin, Michelle Meringer, Christianne Hoey, Jessica Ray, Paul C Boutros, Hon S Leong and 1 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

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  9. IL1R1Nature communications · 2023
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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

11 authors.

Aruz MesciSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Fabrice LucienMayo Clinic Cancer Centre, Rochester, MN, USA.
Xiaoyong HuangSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Eric H WangSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
David ShinSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Michelle MeringerSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Christianne HoeySunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Jessica RaySunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Paul C BoutrosDepartment of Medical Biophysics, University of Toronto, Toronto, Canada.
Hon S LeongMayo Clinic Cancer Centre, Rochester, MN, USA.
Stanley K LiuSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. stanley.liu@sunnybrook.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWhile prostate cancer can often manifest as an indolent disease, the development of locally-advanced or metastatic disease can cause significant morbidity or mortality. Elucidation of molecular mechanisms contributing to disease progression is crucial for more accurate prognostication and effective treatments. R-Spondin 3 (RSPO3) is a protein previously implicated in the progression of colorectal and lung cancers. However, a role for RSPO3 in prostate cancer prognosis and behaviour has not been explored.

methodsWe compare the relative levels of RSPO3 expression between normal prostate tissue and prostate cancer in two independent patient cohorts (Taylor and GSE70768-Cambridge). We also examine the association of biochemical relapse with RSPO3 levels in these cohorts. For elucidation of the biological effect of RSPO3, we use siRNA technology to reduce the levels of RSPO3 in established prostate cancer cell lines, and perform in vitro proliferation, invasion, western blotting for EMT markers and clonogenic survival assays for radiation resistance. Furthermore, we show consequences of RSPO3 knockdown in an established chick chorioallantoic membrane (CAM) assay model of metastasis.

resultsRSPO3 levels are lower in prostate cancer than normal prostate, with a tendency for further loss in metastatic disease. Patients with lower RSPO3 expression have lower rates of biochemical relapse-free survival. SiRNA-mediated loss of RSPO3 results in no change to clonogenic survival and a lower proliferative rate, but increased invasiveness in vitro with induction of epithelial-mesenchymal transition (EMT) markers. Consistent with these results, lower RSPO3 expression translates to greater metastatic capacity in the CAM assay. Together, our preclinical findings identify a role of RSPO3 downregulation in prostate cancer invasiveness, and provide a potential explanation for how RSPO3 functions as a positive prognostic marker in prostate cancer.

Indexed as

AnimalsBiomarkers, TumorCell Line, TumorCell ProliferationChickensDisease-Free SurvivalHumansMaleNeoplasm InvasivenessPrognosisProstatic NeoplasmsR-SpondinsThrombospondinsBiomarkers, TumorRSPO3 protein, humanR-SpondinsThrombospondinsBiochemical relapseInvasionProstate cancerRSPO3

Identifiers

PMID30987640
PMCPMC6466739

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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.