Abstract
ObjectivesTo investigate the expression and prognostic value of bone sialoprotein (BSP) in glioma patients.MethodsWe 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.ResultsBoth 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 O6-methylguanine (O6-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.ConclusionHigh 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.
Highlights
Gliomas are the most common primary tumors in the central nervous system (CNS) and malignant gliomas, which account for 70% of gliomas, are the most frequent and lethal cancers originating in the CNS with a high recurrence and mortality rate [1]
Our study has shown that bone sialoprotein (BSP) is overexpressed in certain glioma tissues and high BSP expression correlates with tumor grade and predicts a poorer survival of glioma patients
In grade IV glioma patients, we found that the median progression-free survival (PFS) of those patients with low BSP expression was 11 months, which was longer that of glioblastoma multiforme (GBM) patients with high BSP expression (8 months) (P = 0.006) (Figure 3C)
Summary
Gliomas are the most common primary tumors in the central nervous system (CNS) and malignant gliomas, which account for 70% of gliomas, are the most frequent and lethal cancers originating in the CNS with a high recurrence and mortality rate [1]. The most biologically aggressive subtype of gliomas is glioblastoma multiforme (GBM) [World Health Organization (WHO) grade IV astrocytoma], a tumor associated with a rather dismal prognosis. Despite the best available therapeutic regimen, the life expectancy of patients with GBM and anaplastic astrocytoma (WHO grade III) is still short, with a median survival of approximately only 14–16 months and 2–5 years, respectively [2]. Substantial efforts have been made in the identification of genetic alterations or molecular markers in GBMs that could help identify subgroups of GBM patients with differing prognoses or clinical response to specific therapies. One of the major determinants of clinical response to temozolomide is the methylation status of the promoter region of O6-methylguanine (O6-meG) DNA methyltransferase (MGMT). The hypermethylation of MGMT promoter is seen in approximately 40% to 60% of patients and correlates with a favorable response to temozolomide
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