Sphingosine kinase 1 is associated with gastric cancer progression and poor survival of patients.
OBJECTIVE
The present study was to investigate the clinical significance of sphingosine kinase 1 (SPHK1), an oncoenzyme, in the development and progression of gastric cancer.


METHODS
mRNA and protein levels of SPHK1 expression in normal gastric epithelial cells, gastric cancer cell lines, and paired gastric cancer lesions and the adjacent noncancerous tissues were examined using reverse transcription-PCR and Western blotting. Immunohistochemistry was employed to analyze SPHK1 expression in 175 clinicopathologically characterized gastric cancer cases. Statistical analyses were applied to derive prognostic and diagnostic associations.


RESULTS
Levels of SPHK1 mRNA and protein were higher in gastric cancer cell lines than in normal gastric epithelial cells. SPHK1 protein level was up-regulated in gastric cancer lesions compared with that in the paired adjacent noncancerous tissues. Gastric cancer tissues from 115 of 175 (65.7%) patients revealed high level of SPHK1 protein expression in contrast to the undetectable or marginally detectable expression of SPHK1 in the adjacent noncancerous gastric tissues. Significantly different expression levels of SPHK1 were found in patients at different clinical stages (P=0.003), T classification (P=0.035), and M classification (P=0.020). Patients with higher SPHK1 expression had shorter overall survival time, whereas those with lower SPHK1 expression survived longer. Further multivariate analysis suggested that SPHK1 up-regulation was an independent prognostic indicator for the disease.


CONCLUSIONS
SPHK1 protein could be a useful marker for the prognosis of gastric cancer. Further study on the potential use of SPHK1 as a therapeutic target is also warranted.
Li
Wen
W
State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Guangzhou, China.
Yu
Chun-Ping
CP
Xia
Jin-tang
JT
Zhang
Ling
L
Weng
Gui-Xiang
GX
Zheng
Hai-qing
HQ
Kong
Qing-li
QL
Hu
Li-juan
LJ
Zeng
Mu-Sheng
MS
Zeng
Yi-xin
YX
Li
Mengfeng
M
Li
Jun
J
Song
Li-Bing
LB
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000032:analysis* / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000099157:Sphingosine Kinase
D014408:Biomarkers, Tumor; D017853:Phosphotransferases (Alcohol Group Acceptor); D012333:RNA, Messenger; D000099157:Sphingosine Kinase