Increased xCT Expression Correlates With Tumor Invasion and Outcome in Patients With Glioblastomas
Increased xCT Expression Correlates With Tumor Invasion and Outcome in Patients With Glioblastomas
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DOI：
10.1227/neu.0b013e318276b2de
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发表时间：
2013-01-01
期刊：
影响因子：
4.8
通讯作者：
Nawashiro, Hiroshi
中科院分区：
文献类型：
--
作者：
Takeuchi, Satoru;Wada, Kojiro;Nawashiro, Hiroshi
背景：xCT是胱氨酸/谷氨酸反转运系统x(c)（-）的轻链。由系统x(c)（-）释放的谷氨酸在胶质母细胞瘤（GBM）细胞浸润中起重要作用。此外，系统x(c)（-）增加谷胱甘肽合成可能保护肿瘤细胞免受放疗和化疗引起的氧化应激。目的：探讨xCT表达水平与GBMs患者mri浸润成像表型及预后的相关性。方法：40例组织学证实的原发性GBMs患者纳入研究。回顾性回顾患者图表，包括年龄、性别、Karnofsky性能状态量表评分、迷你精神状态检查评分、磁共振成像特征、xCT表达、异柠檬酸脱氢酶1 R132H表达、o6 -甲基鸟嘌呤dna甲基转移酶启动子甲基化状态、手术类型、无进展生存期和总生存期。结果：在侵袭性切缘，20例患者的xCT表达弱，20例患者的xCT表达强。Cox回归模型显示，Karnofsky性能状态量表评分低于60分（风险比[HR]: 4.525, P = 0.01）、部分切除（风险比[HR]: 2.839, P = 0.03）和强xCT表达（风险比：4.134,P < 0.001）与较短的无进展生存期显著相关；部分切除（风险比：2.865,P = 0.03）、弱异柠檬酸脱氢酶1 R132H表达（风险比：15.729,P = 0.01）和强xCT表达（风险比：2.863,P = 0.01）与较短的无进展生存期显著相关；P = .04)与较短的总生存期显著相关。结论：这些发现提示xCT是GBMs的独立预测因素。
BACKGROUND: xCT is a light chain of the cystine/glutamate antiporter system x(c)(-). Glutamate that is released by system x(c)(-) plays an important role in the infiltration of glioblastoma (GBM) cells. Furthermore, increased glutathione synthesis by system x(c)(-) may protect tumor cells against oxidative stress induced by radiotherapy and chemotherapy.OBJECTIVE: To investigate whether the levels of xCT expression correlated with infiltrative imaging phenotypes on magnetic resonance imaging and outcomes in patients with GBMs.METHODS: Forty patients with histologically confirmed primary GBMs were included in the study. Patient charts were retrospectively reviewed for age, sex, Karnofsky Performance Status Scale score, Mini-Mental State Examination score, magnetic resonance imaging features, xCT expression, isocitrate dehydrogenase 1 R132H expression, O6-methylguanine-DNA methyltransferase promoter methylation status, type of surgery, progression-free survival, and overall survival.RESULTS: In invasive margins, xCT expression was weak in 20 patients and strong in 20 patients. A Cox regression model revealed that a Karnofsky Performance Status Scale score less than 60 (hazard ratio [HR]: 4.525; P = .01), partial removal (HR: 2.839; P = .03), and strong xCT expression (HR: 4.134; P < .001) were significantly associated with shorter progression-free survival and that partial removal (HR: 2.865; P = .03), weak isocitrate dehydrogenase 1 R132H expression (HR: 15.729; P = .01), and strong xCT expression (HR: 2.863; P = .04) were significantly associated with shorter overall survival.CONCLUSION: These findings suggest that xCT is an independent predictive factor in GBMs.