The expression level of sphingosine-1-phosphate receptor type 1 is related to MIB-1 labeling index and predicts survival of glioblastoma patients

Abstract

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.

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

“…Previous studies have shown that S1P‐SIPRs signaling can enhance cell proliferation and migration. The high S1PR1 expression in glioblastoma patients was positively associated with favorable survival 42. However, S1PR2 signaling negatively regulates tumor angiogenesis and tumor growth in vivo 43.…”

Ki-67 is a Valuable Prognostic Factor in Gliomas: Evidence from a Systematic Review and Meta-analysis

“…Of the candidate studies, 13 articles failed to completely describe the available survival data. Finally, 51 published studies in total were included in the analysis after eliminating articles unsatisfying the selection criteria and duplicates (Jaros et al, 1992;Torp et al, 1992;Montine et al, 1994;Ellison et al, 1995;Heegaard et al, 1995;Kros et al, 1996;Coons et al, 1997;Pollack et al, 1997;Dehghani et al, 1998;McKeever et al, 1998;Ritter et al, 1998;Figarella-Branger et al, 2000;Rodriguez-Pereira et al, 2000;Ho et al, 2001;ReaveyCantwell et al, 2001;Zhong et al, 2001;Bredel et al, 2002;Pollack et al, 2002;Bowers, 2003;Chiang et al, 2003;Neder et al, 2003;Wessels et al, 2003;Zamecnik et al, 2003;Preusser et al, 2005;Uematsu et al, 2005;Kleinschmidt-DeMasters et al, 2006;Donato et al, 2007;Kanamori et al, 2008;Kuo et al, 2009;Laks et al, 2009;Li et al, 2009;Armstrong et al, 2010;Nabika et al, 2010;Watanabe et al, 2010;Yoshida et al, 2010;Habberstad et al, 2011;Margraf et al, 2011;Qiang et al, 2011;Shen et al, 2011;Zawrocki et al, 2011;…”

Re-Configuration of Sphingolipid Metabolism by Oncogenic Transformation

“…In-turn, S1P 1 signalling is necessary for persistent Stat3 activation, forming a positive feedback loop, both within the tumour cells and in the stromal support cells, that fuels the development and growth of melanoma or bladder tumour xenografts, as well as inflammation-induced colon cancer [71,124]. In an interesting contrast to these findings, expression of the S1P 1 receptor suppresses glioblastoma growth and malignancy, despite the established association of SPHK1 with increased glioblastoma malignancy [92,125,126]. …”