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谷氨酸代谢型受体在肾细胞癌风险和生存中的临床意义。

Clinical significance of glutamate metabotropic receptors in renal cell carcinoma risk and survival.

机构信息

Department of Urology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.

Department of Urology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.

出版信息

Cancer Med. 2018 Dec;7(12):6104-6111. doi: 10.1002/cam4.1901. Epub 2018 Nov 28.

DOI:10.1002/cam4.1901
PMID:30488581
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6308098/
Abstract

Accumulating evidence suggests the roles of glutamate metabotropic receptors (GRMs) in cancer, in addition to synaptic signalling. The present study assessed the associations of genetic variants in eight GRM genes with regard to risk and overall survival (OS) in 780 renal cell carcinoma (RCC) patients and controls. After adjustment for known risk factors, GRM5 rs7102764 T was associated with an increased risk of RCC (P = 0.006). Additional analysis has provided evidence that rs7102764 T was correlated with a higher expression of GRM5, which is consistently found to be upregulated in tumours, compared to normal tissues. Furthermore, the GRM3 rs701332 C, GRM4 rs2499707 T, and GRM4 rs4713742 T alleles were significantly associated with a poorer OS (P ≤ 0.030). The three loci were also observed to have strong cumulative effects on OS. Additional analysis has revealed a significant genotype-expression correlation of rs2499707 T with increased GRM4 expression, which in turn leads to poorer OS in patients with RCC. GRMs might be involved in RCC development and progression, and genetic variants in GRMs might be promising biomarkers.

摘要

越来越多的证据表明，谷氨酸代谢型受体（GRM）除了在突触信号传递中发挥作用外，还在癌症中发挥作用。本研究评估了 780 例肾细胞癌（RCC）患者和对照者的 8 个 GRM 基因中的遗传变异与风险和总生存期（OS）的相关性。在调整了已知的风险因素后，GRM5 rs7102764 T 与 RCC 风险增加相关（P = 0.006）。进一步的分析表明，rs7102764 T 与 GRM5 的表达增加相关，与正常组织相比，GRM5 在肿瘤中持续上调。此外，GRM3 rs701332 C、GRM4 rs2499707 T 和 GRM4 rs4713742 T 等位基因与较差的 OS 显著相关（P ≤ 0.030）。这三个位点也观察到对 OS 有很强的累积效应。进一步的分析显示，rs2499707 T 与 GRM4 表达增加存在显著的基因型-表达相关性，这反过来又导致 RCC 患者的 OS 较差。GRMs 可能参与了 RCC 的发生和发展，GRMs 中的遗传变异可能是有前途的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fd/6308098/ae2302274e9d/CAM4-7-6104-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fd/6308098/b08664ee97ea/CAM4-7-6104-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fd/6308098/b91431ec6436/CAM4-7-6104-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fd/6308098/ae2302274e9d/CAM4-7-6104-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fd/6308098/b08664ee97ea/CAM4-7-6104-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fd/6308098/b91431ec6436/CAM4-7-6104-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fd/6308098/ae2302274e9d/CAM4-7-6104-g003.jpg

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