title: Increased xCT expression correlates with tumor invasion and outcome in patients with glioblastomas.
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.
  
  
  CONCLUSIONS
  These findings suggest that xCT is an independent predictive factor in GBMs.
authors.affiliation: Department of Neurosurgery, National Defense Medical College, Tokorozawa, Saitama, Japan. s.takeuchi@room.ocn.ne.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Kojiro
authors.initials: K
authors.lastname: Wada
authors.forename: Terushige
authors.initials: T
authors.lastname: Toyooka
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shimazaki
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Nagatani
authors.forename: Naoki
authors.initials: N
authors.lastname: Otani
authors.forename: Hideo
authors.initials: H
authors.lastname: Osada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Uozumi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nawashiro
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D027182:Amino Acid Transport System y+ / Q000235:genetics*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D003131:Combined Modality Therapy; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009483:Neuropsychological Tests; D011379:Prognosis; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D027182:Amino Acid Transport System y+; D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; C493397:SLC1A2 protein, human; C118895:SLC7A11 protein, human; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide