PURPOSE: To characterize the expression of sphingosine kinase-1 (SPHK1) in human astrocytomas and to investigate the association between SPHK1 expression and progression of astrocytomas. EXPERIMENTAL DESIGN: The expression of SPHK1 in normal human astrocytes, astrocytoma cell lines, and four pairs of matched astrocytoma tissues and their adjacent normal brain tissues were detected by quantitative reverse transcription-PCR and Western blot. In addition, SPHK1 protein expression was examined in 243 cases of histologically characterized astrocytomas by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. RESULTS: SPHK1 in astrocytoma cell lines was elevated at both mRNA and protein levels, and the SPHK1 mRNA and protein were significantly up-regulated by up to 6.8- and 40-fold, respectively, in primary astrocytomas compared with those in the adjacent noncancerous brain tissues. Immunohistochemical analysis showed that 100 of 243 (41.2%) paraffin-embedded archival astrocytoma biopsies exhibited high expression of SPHK1. Statistical analysis suggested that the up-regulation of SPHK1 was significantly correlated with the histologic grade of astrocytoma (P=0.000) and that patients with high SPHK1 level exhibited shorter survival time (P<0.001). Multivariate analysis revealed that SPHK1 up-regulation might be an independent prognostic indicator for the survival of patients with astrocytoma. CONCLUSIONS: SPHK1 might represent a novel and useful prognostic marker for astrocytoma and play a role during the development and progression of the disease.
PURPOSE: To characterize the expression of sphingosine kinase-1 (SPHK1) in humanastrocytomas and to investigate the association between SPHK1 expression and progression of astrocytomas. EXPERIMENTAL DESIGN: The expression of SPHK1 in normal human astrocytes, astrocytoma cell lines, and four pairs of matched astrocytoma tissues and their adjacent normal brain tissues were detected by quantitative reverse transcription-PCR and Western blot. In addition, SPHK1 protein expression was examined in 243 cases of histologically characterized astrocytomas by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. RESULTS:SPHK1 in astrocytoma cell lines was elevated at both mRNA and protein levels, and the SPHK1 mRNA and protein were significantly up-regulated by up to 6.8- and 40-fold, respectively, in primary astrocytomas compared with those in the adjacent noncancerous brain tissues. Immunohistochemical analysis showed that 100 of 243 (41.2%) paraffin-embedded archival astrocytoma biopsies exhibited high expression of SPHK1. Statistical analysis suggested that the up-regulation of SPHK1 was significantly correlated with the histologic grade of astrocytoma (P=0.000) and that patients with high SPHK1 level exhibited shorter survival time (P<0.001). Multivariate analysis revealed that SPHK1 up-regulation might be an independent prognostic indicator for the survival of patients with astrocytoma. CONCLUSIONS:SPHK1 might represent a novel and useful prognostic marker for astrocytoma and play a role during the development and progression of the disease.
Authors: Andrew J Kennedy; Thomas P Mathews; Yugesh Kharel; Saundra D Field; Morgan L Moyer; James E East; Joseph D Houck; Kevin R Lynch; Timothy L Macdonald Journal: J Med Chem Date: 2011-05-02 Impact factor: 7.446