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Br J Cancer. 2019 Mar;120(6):633-639. doi: 10.1038/s41416-019-0396-7. Epub 2019 Feb 20.

Apelin and apelin receptor expression in renal cell carcinoma.

Author information

1
Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany.
2
Department of Urology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany.
3
Department of Urology, Charite - Universitätsmedizin Berlin, Schumannstrasse 20, 10117, Berlin, Germany.
4
Berlin Institute for Urologic Research, Schumannstrasse 20, 10117, Berlin, Germany.
5
Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany. glen.kristiansen@ukbonn.de.
6
Department of Urology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany. stefan.hauser@ukbonn.de.

Abstract

BACKGROUND:

The APLNR (apelin receptor) has been shown to be an essential gene for cancer immunotherapy, with deficiency in APLNR leading to immunotherapy failure. The aim of this study is to investigate the expression of APLN (apelin) and APLNR in patients with renal cell carcinoma (RCC), and its association with clinicopathological parameters and survival.

METHODS:

Three well-characterised patient cohorts with RCC were used: Study cohort 1 (clear-cell RCC; APLN/APLNR mRNA expression; n = 166); TCGA validation cohort (clear-cell RCC; APLN/APLNR mRNA expression; n = 481); Study cohort 2 (all RCC subtypes; APLNR protein expression/immunohistochemistry; n = 300). Associations between mRNA/protein expression and clinicopathological variables/patients' survival were tested statistically.

RESULTS:

While APLN showed only very weak association with tumour histological grade (TCGA cohort), APLNR/mRNA protein expression correlate significantly with ccRCC aggressiveness. APLNR is expressed in tumour vasculature and tumour cells at different levels, and these expression levels associate with tumour aggressiveness in opposing directions. APLNR expression was negatively correlated with PD-L1 expression by tumour cells in a subset of patients with ccRCC. APLNR expression in either compartment is an independent prognostic factor for survival of patients with ccRCC.

CONCLUSION:

The APLNR/APLN-system appears to play an important role in ccRCC, warranting further clinical investigation.

PMID:
30783205
DOI:
10.1038/s41416-019-0396-7

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