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肾细胞癌中 Apelin 和 Apelin 受体的表达。

Apelin and apelin receptor expression in renal cell carcinoma.

机构信息

Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany.

Department of Urology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany.

出版信息

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

DOI:10.1038/s41416-019-0396-7
PMID:30783205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6461937/
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.

摘要

背景

APLNR（apelin 受体）已被证明是癌症免疫治疗的必需基因，APLNR 缺陷会导致免疫治疗失败。本研究旨在探讨 APLN（apelin）和 APLNR 在肾细胞癌（RCC）患者中的表达及其与临床病理参数和生存的关系。

方法

本研究使用了三个经过充分验证的 RCC 患者队列：研究队列 1（透明细胞 RCC；APLN/APLNR mRNA 表达；n=166）；TCGA 验证队列（透明细胞 RCC；APLN/APLNR mRNA 表达；n=481）；研究队列 2（所有 RCC 亚型；APLNR 蛋白表达/免疫组化；n=300）。统计检验了 mRNA/蛋白表达与临床病理变量/患者生存之间的关系。

结果

虽然 APLN 与肿瘤组织学分级仅有非常微弱的相关性（TCGA 队列），但 APLNR/mRNA 蛋白表达与 ccRCC 的侵袭性显著相关。APLNR 在肿瘤血管和肿瘤细胞中以不同的水平表达，这些表达水平与肿瘤的侵袭性呈相反的方向相关。在 ccRCC 的一部分患者中，APLNR 表达与肿瘤细胞的 PD-L1 表达呈负相关。APLNR 在任何一个部位的表达都是 ccRCC 患者生存的独立预后因素。

结论

APLNR/APLN 系统似乎在 ccRCC 中发挥着重要作用，值得进一步的临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/b00c11238a6b/41416_2019_396_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/7d640d993510/41416_2019_396_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/72e28be3c749/41416_2019_396_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/3844105af49d/41416_2019_396_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/dbbdfdd6d8a5/41416_2019_396_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/b00c11238a6b/41416_2019_396_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/7d640d993510/41416_2019_396_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/72e28be3c749/41416_2019_396_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/3844105af49d/41416_2019_396_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/dbbdfdd6d8a5/41416_2019_396_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f212/6461937/b00c11238a6b/41416_2019_396_Fig5_HTML.jpg

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