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

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

Huang CY1,2, Hsueh YM3,4, Chen LC5, Cheng WC6,7,8, Yu CC9,10,11, Chen WJ12, Lu TL13, Lan KJ13, Lee CH14, Huang SP14,15,16,17, Bao BY13,18,19.

Author information

1
Department of Urology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
2
Department of Urology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
3
Department of Family Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
4
Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
5
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
6
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
7
Research Center for Tumor Medical Science, China Medical University, Taichung, Taiwan.
8
Drug Development Center, China Medical University, Taichung, Taiwa.
9
Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
10
Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
11
Department of Pharmacy, Tajen University, Pingtung, Taiwan.
12
School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
13
Department of Pharmacy, China Medical University, Taichung, Taiwan.
14
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
15
Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
16
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
17
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
18
Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
19
Department of Nursing, Asia University, Taichung, Taiwan.

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.

KEYWORDS:

glutamate metabotropic receptors; prognosis; renal cell carcinoma; single-nucleotide polymorphisms; survival

PMID:
30488581
PMCID:
PMC6308098
DOI:
10.1002/cam4.1901
[Indexed for MEDLINE]
Free PMC Article

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