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

Takeuchi, Satoru MD*; Wada, Kojiro MD*; Toyooka, Terushige MD*; Shinomiya, Nariyoshi MD; Shimazaki, Hideyuki MD§; Nakanishi, Kuniaki MD§; Nagatani, Kimihiro MD*; Otani, Naoki MD*; Osada, Hideo MD*; Uozumi, Yoichi MD*; Matsuo, Hirotaka MD; Nawashiro, Hiroshi MD*

doi: 10.1227/NEU.0b013e318276b2de
Research-Human-Clinical Studies

BACKGROUND: xCT is a light chain of the cystine/glutamate antiporter system xc. Glutamate that is released by system xc plays an important role in the infiltration of glioblastoma (GBM) cells. Furthermore, increased glutathione synthesis by system xc 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.

ABBREVIATIONS: EAAT-2, excitatory amino acid transporter 2

GBM, glioblastoma

GSH, glutathione

IDH1, isocitrate dehydrogenase 1

KPS, Karnofsky Performance Status Scale

MGMT, O6-methylguanine–DNA methyltransferase

MMSE, Mini-Mental Status Examination

OS, overall survival

PFS, progression-free survival

Departments of *Neurosurgery

Integrative Physiology and Bio-Nano Medicine

§Pathology and Laboratory Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan

Correspondence: Satoru Takeuchi, MD, Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. E-mail:

Received March 22, 2012

Accepted September 14, 2012

Copyright © by the Congress of Neurological Surgeons