title: High bone sialoprotein (BSP) expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients.
abstract: OBJECTIVE
  To investigate the expression and prognostic value of bone sialoprotein (BSP) in glioma patients.
  
  
  METHODS
  We determined the expression of BSP using real-time RT-PCR and immunohistochemistry in tissue microarrays containing 15 normal brain and 270 glioma samples. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate analyses were performed by the stepwise forward Cox regression model.
  
  
  RESULTS
  Both BSP mRNA and protein levels were significantly elevated in high-grade glioma tissues compared with those of normal brain and low-grade glioma tissues, and BSP expression positively correlated with tumor grade (P<0.001). Univariate and multivariate analysis showed high BSP expression was an independent prognostic factor for a shorter progression-free survival (PFS) and overall survival (OS) in both grade III and grade IV glioma patients [hazard ratio (HR) = 2.549 and 3.154 for grade III glioma, and HR = 1.637 and 1.574 for grade IV glioma, respectively]. Patients with low BSP expression had a significantly longer median OS and PFS than those with high BSP expression. Small extent of resection and lineage of astrocyte served as independent risk factors of both shorter PFS and OS in grade III glioma patients; GBM patients without O(6)-methylguanine (O(6)-meG) DNA methyltransferase (MGMT) methylation and Karnofsky performance score (KPS) less than 70 points were related to poor prognosis. Lack of radiotherapy related to shorter OS but not affect PFS in both grade III and grade IV glioma patients.
  
  
  CONCLUSIONS
  High BSP expression occurs in a significant subset of high-grade glioma patients and predicts a poorer outcome. The study identifies a potentially useful molecular marker for the categorization and targeted therapy of gliomas.
authors.affiliation: Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Rong
authors.initials: R
authors.lastname: Qin
authors.forename: Jinxu
authors.initials: J
authors.lastname: Zhou
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Lu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Da
authors.initials: D
authors.lastname: Fu
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Lv
authors.forename: Weiqing
authors.initials: W
authors.lastname: Li
authors.forename: Chunyan
authors.initials: C
authors.lastname: Xia
authors.forename: Guohan
authors.initials: G
authors.lastname: Hu
authors.forename: Xuehua
authors.initials: X
authors.lastname: Ding
authors.forename: Juxiang
authors.initials: J
authors.lastname: Chen
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D058574:Integrin-Binding Sialoprotein