Clinical significance of glutamate metabotropic receptors in renal cell carcinoma risk and survival.
Clinical significance of glutamate metabotropic receptors in renal cell carcinoma risk and survival.
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谷氨酸代谢受体在肾细胞癌风险和生存中的临床意义。
DOI：
10.1002/cam4.1901
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发表时间：
2018-12
期刊：
影响因子：
4
通讯作者：
Bao BY
中科院分区：
文献类型：
--
作者：
Huang CY;Hsueh YM;Chen LC;Cheng WC;Yu CC;Chen WJ;Lu TL;Lan KJ;Lee CH;Huang SP;Bao BY
越来越多的证据表明，谷氨酸代谢型受体（GRM）在癌症中的作用，除了突触信号。本研究评估了780例肾细胞癌（RCC）患者和对照组中8个GRM基因的遗传变异与风险和总生存期（OS）的相关性。校正已知危险因素后，GRM5 rs7102764 T与RCC风险增加相关（P = 0.006）。额外的分析提供了证据表明，rs7102764 T与GRM5的更高表达相关，与正常组织相比，GRM5在肿瘤中一直被发现上调。此外，GRM3 rs701332 C、GRM4 rs2499707 T和GRM4 rs4713742 T等位基因与OS较差显著相关（P ≤ 0.030）。还观察到这三个位点对OS具有强烈的累积效应。额外的分析揭示了rs2499707 T与GRM4表达增加的显著基因型表达相关性，这反过来导致RCC患者的OS较差。GRM可能参与肾细胞癌的发生和发展，GRM的遗传变异可能是有前途的生物标志物。
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.
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