title: High-mobility group box 2 is associated with prognosis of glioblastoma by promoting cell viability, invasion, and chemotherapeutic resistance.
abstract: BACKGROUND
  The expression profile of high-mobility group box 2 (HMGB2) in patients with glioblastoma multiforme (GBM) and its clinical signature with underlying mechanisms were not fully explored.
  
  
  METHODS
  HMGB2 protein levels were measured in 51 GBM patients by immunohistochemical studies. To clarify the precise role of HMGB2 on cell invasion and viability of 3 GBM cell lines, we did in vitro and in vivo analyses with lentivirus vectors and small interfering RNA. Transwell invasion assays and wound-healing assays were used to analyze the invasion of GBM cells. Expression of p53 and matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot.
  
  
  RESULTS
  HMGB2 protein expression was significantly higher in GBM than in controlled brain tissues (P < .0001). HMGB2 overexpression was significantly correlated with shorter overall survival time, which was the only independent prognostic factor for overall survival in a multivariate analysis (P = .017). HMGB2 knockdown by small interfering RNA decreased cell viability and invasion in vitro and significantly decreased tumor volume in vivo, which might be involved in the change of p53 expression and the balance of MMP2/TIMP2. Moreover, silencing of HMGB2 could significantly increase the sensitivity of GBM cells to temozolomide chemotherapy.
  
  
  CONCLUSIONS
  Our present data suggest that HMGB2 expression is a significant prognostic factor and might play an important role in cell invasion and temozolomide-induced chemotherapeutic sensitivity of GBM. This study highlights the importance of HMGB2 as a novel prognostic marker and an attractive therapeutic target of GBM.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhe Bao
authors.initials: ZB
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Shao Jian
authors.initials: SJ
authors.lastname: Lin
authors.forename: Zhen Kun
authors.initials: ZK
authors.lastname: Xiong
authors.forename: Jiang Long
authors.initials: JL
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.forename: Liang Fu
authors.initials: LF
authors.lastname: Zhou
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D024261:HMGB2 Protein / Q000378:metabolism*; D006801:Humans; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D024261:HMGB2 Protein
keywords: glioblastoma; high-mobility group box 2; invasion; prognosis; temozolomide