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. 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

Chao-Yuan Huang  1   2 , Yu-Mei Hsueh  3   4 , Lih-Chyang Chen  5 , Wei-Chung Cheng  6   7   8 , Chia-Cheng Yu  9   10   11 , Wei-Jen Chen  12 , Te-Ling Lu  13 , Kuo-Jin Lan  13 , Cheng-Hsueh Lee  14 , Shu-Pin Huang  14   15   16   17 , Bo-Ying Bao  13   18   19
Affiliations

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

Chao-Yuan Huang et al. Cancer Med. 2018 Dec.

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.

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Figures

Figure 1
Figure 1
Impact of genetic variants of GRM3 and GRM4 on renal cell carcinoma (RCC) survival. Kaplan‐Meier curves of overall survival for RCC patients with 0, 1‐2, or >2 risk alleles (GRM3 rs701332 C, GRM4 rs2499707 T, and GRM4 rs4713742 T). The numbers in parentheses indicate the number of patients
Figure 2
Figure 2
The expression quantitative trait loci analysis of GRM SNPs and gene expression levels. Correlations of (A) rs7102764 genotypes with GRM5 expression, (B) rs701332 genotypes with GRM3 expression, (C) rs2499707 genotypes with GRM4 expression, and (D) rs4713742 genotypes with GRM4 expression. The numbers in parentheses indicate the number of patients
Figure 3
Figure 3
Roles of GRM3, GRM4, and GRM5 expression in renal cell carcinoma (RCC) progression. GRM3, GRM4, and GRM5 expression levels in (A) normal and tumour tissues, (B) different stages, and (C) different grades of RCC. (D) Kaplan‐Meier curves of overall survival according to GRM3, GRM4, and GRM5 expression levels. Patients were dichotomised at the mean gene expression level into the low and high groups. The numbers in parentheses indicate the number of patients
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