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. 2012;7(10):e48415.
doi: 10.1371/journal.pone.0048415. Epub 2012 Oct 31.

High bone sialoprotein (BSP) expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients

Tao Xu  1 , Rong Qin, Jinxu Zhou, Yong Yan, Yicheng Lu, Xiaoping Zhang, Da Fu, Zhongwei Lv, Weiqing Li, Chunyan Xia, Guohan Hu, Xuehua Ding, Juxiang Chen
Affiliations

High bone sialoprotein (BSP) expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients

Tao Xu et al. PLoS One. 2012.

Abstract

Objectives: 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.

Conclusion: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Survival and BSP expression pattern of glioma patients.
The progression-free survival curve (A) and overall survival curve (B) in all 270 glioma patients (indicated in black) and 162 high-grade glioma patients (indicated in red). (C) Quantitative RT–PCR assays and (D) immunohistochemical staining showed that high-grade glioma (HGG) tissues expressed significantly higher levels of BSP mRNA transcripts and protein than low-grade glioma (LGG) and normal brain (NB) tissues. Data is expressed as Mean ± SE and the differences among groups were determined using Mann-Whitney U test (# P>0.05, LGG vs. NB).
Figure 2
Figure 2. Immunohistochemical staining of BSP in glioma and normal brain tissues.
Immunohistochemical staining of BSP in normal brain tissue (A, B, staining intensity score = 2), grade I pilocytic astrocytoma (C, staining intensity score = 3), grade II astrocytoma (D, staining intensity score = 3), grade II oligodendroglioma (E, staining intensity score = 3), grade III anaplastic oligodendroglioma (F, staining intensity score = 6) and grade III anaplastic astrocytoma (G, staining intensity score = 6) and grade IV (H, staining intensity score = 9) glioma tissue specimens.
Figure 3
Figure 3. High BSP expression is associated shorter overall survival and progression-free survival of WHO grade III and IV glioma patients.
The progression-free survival (A) and Kaplan-Meier survival curve (B) for WHO grade III glioma patients stratified by BSP expression. The progression-free survival (C) and Kaplan-Meier survival curve (D) for WHO grade IV glioma patients stratified by BSP expression.
Figure 4
Figure 4. Multivariate analysis of factors associated with survival and progression of WHO grade III and IV glioma patients.
Hazard ratio and 95% CIs for factors that related to OS (A) and PFS (B) in WHO grade III glioma patients, OS (C) and PFS (D) in WHO grade IV glioma patients.
See this image and copyright information in PMC

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