Increased xCT expression correlates with tumor invasion and outcome in patients with glioblastomas

Neurosurgery. 2013 Jan;72(1):33-41; discussion 41. doi: 10.1227/NEU.0b013e318276b2de.

Abstract

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, O-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Amino Acid Transport System y+ / genetics*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Biomarkers, Tumor
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery*
  • Combined Modality Therapy
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Disease-Free Survival
  • Female
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Glioblastoma / surgery*
  • Glutamate Plasma Membrane Transport Proteins / genetics
  • Humans
  • Immunohistochemistry
  • Isocitrate Dehydrogenase / genetics
  • Kaplan-Meier Estimate
  • Karnofsky Performance Status
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neuropsychological Tests
  • Prognosis
  • Survival Analysis
  • Temozolomide
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics
  • Young Adult

Substances

  • Amino Acid Transport System y+
  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • Glutamate Plasma Membrane Transport Proteins
  • SLC1A2 protein, human
  • SLC7A11 protein, human
  • Tumor Suppressor Proteins
  • Dacarbazine
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide