Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R China.
Mol Med Rep. 2018 Mar;17(3):4651-4656. doi: 10.3892/mmr.2018.8404. Epub 2018 Jan 9.
The present study aimed to investigate the location, expression and clinical significance of Iroquois homeobox gene (IRX1) in human glioma. The expression of IRX1 gene in glioma cell lines (U87, U373, LN229 and T98G) and normal brain tissue was detected via reverse transcription-polymerase chain reaction. The IRX1 protein in fresh glioma specimens, with the adjacent normal brain tissue, was quantified through western blotting. The archived glioma only specimens from the present hospital and glioma specimens with adjacent normal brain tissue, from Alenabio biotechnology, were subjected to immunohistochemistry and tissue microarray analysis, respectively. The Kaplan-Meier method was employed to assess the correlation between the IRX1 level and the overall survival time of the patients. IRX1 gene was demonstrated to be expressed at varying levels in U373, LN229 and T98G cells, however not in U87 cells and normal brain tissue. Western blotting revealed increased IRX1 expression in glioma tissue compared with adjacent normal brain tissue. Furthermore, a direct correlation was observed between the IRX1 expression and the clinical glioma grade, with a significant difference in the gene expression between high grade and low grade glioma (P<0.05). Notably, IRX1 was identified to be localized to the cytoplasm in the adjacent normal brain and World Health Organization grade I glioma, whereas was identified to be present in the nucleus in higher grade glioma. In addition to being established as a significant prognostic variable, IRX1 expression was positively correlated with the overall survival of glioma patients. IRX1 gene may therefore exhibit an oncogenic role in glioma condition, and thus may be of clinical importance as a future therapeutic target.
本研究旨在探讨同源异型盒基因（IRX1）在人脑胶质瘤中的定位、表达及临床意义。采用逆转录-聚合酶链反应检测 IRX1 基因在胶质瘤细胞系（U87、U373、LN229 和 T98G）和正常脑组织中的表达。采用 Western blot 法检测新鲜脑胶质瘤标本及其毗邻正常脑组织中 IRX1 蛋白的表达。采用免疫组织化学和组织微阵列分析分别对本医院存档的脑胶质瘤标本和 Alenabio 生物技术公司的脑胶质瘤毗邻正常脑组织标本进行分析。采用 Kaplan-Meier 法评估 IRX1 水平与患者总生存时间的相关性。结果显示，IRX1 基因在 U373、LN229 和 T98G 细胞中呈不同水平表达，但在 U87 细胞和正常脑组织中不表达。Western blot 法显示，与毗邻正常脑组织相比，脑胶质瘤组织中 IRX1 表达增加。此外，IRX1 表达与临床胶质瘤分级呈正相关，高级别和低级别胶质瘤之间基因表达差异有统计学意义（P<0.05）。值得注意的是，IRX1 在毗邻正常脑组织和 World Health Organization 分级 I 级胶质瘤中定位于细胞质，而在高级别胶质瘤中定位于细胞核。IRX1 表达不仅被确定为显著的预后变量，而且与胶质瘤患者的总生存时间呈正相关。因此，IRX1 基因在胶质瘤中可能发挥致癌作用，作为未来的治疗靶点具有重要的临床意义。
