Abstract
BackgroundThe 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.MethodsThree 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.ResultsWhile 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.ConclusionThe APLNR/APLN-system appears to play an important role in ccRCC, warranting further clinical investigation.
Highlights
The APLNR has been shown to be an essential gene for cancer immunotherapy, with deficiency in APLNR leading to immunotherapy failure
Given the paucity of data concerning the role of APLN and APLNR in renal cell carcinoma[12] and the importance of immune evasion mechanisms of this tumour, our study aimed to investigate the expression of APLN and APLNR in RCC and its association with clinicopathological parameters and survival
APLNR was predictive for overall (OS) and cancer-specific survival (CSS) in Kaplan–Meier (Fig. 2a, b), univariate (OS: HR 3.5, 95% CI 1.7–7.0, p = 0.0006; CSS: HR 4.1, 95% CI 1.7–9.7, p = 0.001) and multivariate Cox analyses of mRNA expression, histological grade and pT-stage (OS: HR 2.9, 95% CI 1.4–5.8, p = 0.004; CSS: HR 3.5, 95% CI 1.5–8.4, p = 0.001), with lower expression predicting shorter survival times
Summary
The APLNR (apelin receptor) has been shown to be an essential gene for cancer immunotherapy, with deficiency in APLNR leading to immunotherapy failure. The apelin receptor (coded by the APLNR gene) was identified as prerequisite for successful cancer immunotherapy, with APLNR deficiency associated with immunotherapy failure.[5] Since apelin (APLN) and the apelin receptor have long been known to play important roles in vascular physiology,[6,7] emerging evidence of their importance in oncological diseases is not surprising.[8,9,10,11] Given the paucity of data concerning the role of APLN and APLNR in renal cell carcinoma[12] and the importance of immune evasion mechanisms of this tumour, our study aimed to investigate the expression of APLN and APLNR in RCC and its association with clinicopathological parameters and survival
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