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谷氨酸受体离子型钾通道3(GRIK3):一种与胃癌肿瘤TNM分期、淋巴结转移及不良预后相关的新型致癌蛋白。

GRIK3: A novel oncogenic protein related to tumor TNM stage, lymph node metastasis, and poor prognosis of GC.

作者信息

Gong Baocheng, Li Yuan, Cheng Zhenguo, Wang Pengliang, Luo Lei, Huang Hanwei, Duan Shijie, Liu Funan

机构信息

1 Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China.

2 Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, Shenyang, China.

出版信息

Tumour Biol. 2017 Jun;39(6):1010428317704364. doi: 10.1177/1010428317704364.

DOI:10.1177/1010428317704364
PMID:28631555
Abstract

Glutamate receptor, ionotropic, kainate 3 (GRIK3), as a member of the glutamate kainate receptor family, mainly participated in neuroactive ligand receptor interaction pathway. Other members of GRIK family were previously reported to regulate cellular migration, transformation, and proliferation in tumor. However, the mechanism of GRIK3 in tumor is still unclear. Therefore, the purpose of our study was to reveal the expression and clinical significance of GRIK3 in gastric cancer (GC). First, we performed the expression analysis and survival analysis of GRIK3 using The Cancer Genome Atlas (TCGA) database, and the results showed that the GRIK3 expressed differentially between gastric cancer tissues and the adjacent normal tissues and that higher expression of GRIK3 was associated with poor survival outcomes. And the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that GRIK3 mainly took part in cancer-related process. Subsequently, the validated immunohistochemistry showed that GRIK3 expressed higher in the GC tissues than in the matched normal tissues and the patients with overexpressed GRIK3 had worse survival outcomes. The univariate and multivariate analyses suggested that the expression of GRIK3 was an independent prognostic factor to predict GC prognosis. Furthermore, additional experiment showed that the lymph node metastasis tissues had higher GRIK3 expression than their matched primary GC tissues. These findings suggested that elevated GRIK3 expression could serve as an independent prognostic biomarker and a novel potential treatment target for patients with GC.

摘要

离子型红藻氨酸盐受体3(GRIK3)作为红藻氨酸盐谷氨酸受体家族的一员,主要参与神经活性配体受体相互作用途径。先前有报道称,GRIK家族的其他成员可调节肿瘤细胞的迁移、转化和增殖。然而,GRIK3在肿瘤中的作用机制仍不清楚。因此,我们研究的目的是揭示GRIK3在胃癌(GC)中的表达及临床意义。首先,我们使用癌症基因组图谱(TCGA)数据库对GRIK3进行了表达分析和生存分析,结果显示GRIK3在胃癌组织和相邻正常组织中的表达存在差异,且GRIK3的高表达与较差的生存结果相关。基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析表明,GRIK3主要参与癌症相关过程。随后,经过验证的免疫组织化学显示,GRIK3在GC组织中的表达高于配对的正常组织,且GRIK3过表达的患者生存结果更差。单因素和多因素分析表明,GRIK3的表达是预测GC预后的独立预后因素。此外,额外的实验表明,淋巴结转移组织中GRIK3的表达高于其配对的原发性GC组织。这些发现表明,GRIK3表达升高可作为GC患者独立的预后生物标志物和新的潜在治疗靶点。

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