Increased xCT Expression Correlates With Tumor Invasion and Outcome in Patients With Glioblastomas

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.