The expression level of sphingosine-1-phosphate receptor type 1 is related to MIB-1 labeling index and predicts survival of glioblastoma patients.
Although there are many reports on the clinical use of the MIB-1 labeling index (LI), which is a measure of proliferative activity in astrocytomas; its significance varies between studies. There are no known molecules that are directly linked to the MIB-1 LI in astrocytomas. We evaluated the clinical value of the MIB-1 LI in our human glioblastoma cases and determined the molecules that possibly influenced the MIB-1 LI. An immunohistochemical study of the MIB-1 protein was performed and MIB-1 LIs of 38 glioblastomas were determined. In the same cases, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-alpha (PDGFRA), and sphingosine-1-phosphate receptor type 1 (S1P(1)), which are known regulators of glioma cell proliferation, were detected and quantified by quantitative real-time-PCR or western blotting. Kaplan-Meier survival curves for 38 patients with glioblastomas showed that a high MIB-1 LI correlated with poor survival (P < 0.05). Among the molecules tested, only the low expression of S1P(1) was significantly correlated with the high MIB-1 LI in glioblastomas (P < 0.05). Multivariate analysis revealed that the S1P(1) expression level was a significant prognostic factor. Our results indicate that the MIB-1 LI is an important prognostic factor in human glioblastomas. Furthermore, downregulation of S1P(1) expression increases proliferative activity, and thus enhances the malignancy of glioblastomas, resulting in a poor survival.
Yoshida
Yuya
Y
Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
Nakada
Mitsutoshi
M
Harada
Tomoya
T
Tanaka
Shingo
S
Furuta
Takuya
T
Hayashi
Yasuhiko
Y
Kita
Daisuke
D
Uchiyama
Naoyuki
N
Hayashi
Yutaka
Y
Hamada
Jun-ichiro
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001932:Brain Neoplasms / Q000145:classification / Q000378:metabolism* / Q000401:mortality*; D002648:Child; D005260:Female; D005909:Glioblastoma / Q000145:classification / Q000378:metabolism* / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D000081025:Sphingosine-1-Phosphate Receptors; D013223:Statistics as Topic; D055815:Young Adult
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; C440408:MIB-1 antibody; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors