Clinical significance of sphingosine kinase-1 expression in human astrocytomas progression and overall patient survival.
OBJECTIVE
To characterize the expression of sphingosine kinase-1 (SPHK1) in human astrocytomas and to investigate the association between SPHK1 expression and progression of astrocytomas.


METHODS
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.
Li
Jun
J
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
Guan
Hong-Yu
HY
Gong
Li-Yun
LY
Song
Li-Bing
LB
Zhang
Nu
N
Wu
Jueheng
J
Yuan
Jie
J
Zheng
Yi-Jie
YJ
Huang
Zheng-Song
ZS
Li
Mengfeng
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000378:metabolism* / Q000401:mortality*; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis; D000099157:Sphingosine Kinase
D014408:Biomarkers, Tumor; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase