Skip to main content
Top
Published in: Medical Oncology 11/2014

01-11-2014 | Original Paper

High expression of SPHK1 in sacral chordoma and association with patients’ poor prognosis

Authors: Kai Zhang, Hao Chen, Guizhong Wu, Kangwu Chen, Huilin Yang

Published in: Medical Oncology | Issue 11/2014

Login to get access

Abstract

Sacral chordoma is an aggressive bone tumor with a high local recurrence rate. Surgery remains the standard treatment because of its resistance to chemotherapy and radiotherapy. However, recurrence occurs frequently even after complete surgical resection. Great effort has been invested in discovering novel biomarkers and therapeutic targets. To date, the molecular mechanism is still unclear. In this study, we evaluated the expression of sphingosine kinase 1 (SPHK1) in 42 sacral chordoma samples and 16 distant normal tissue specimens by immunohistochemical staining. In addition, we analyzed its association with the clinical factors and patients’ prognosis. Of all the chordoma samples, 69 % (29/42) showed high expression of SPHK1, whereas, only 19 % (3/16) of distant normal tissues expressed a high level of SPHK1 (p = 0.001). Chi-square analysis revealed that high expression of SPHK1 was significantly correlated with tumor recurrence (p = 0.019) and invasion into surrounding muscle (p = 0.005), while the data did not indicate any association with patients’ gender, age, tumor location and size (p > 0.05). Kaplan–Meier survival curve and log-rank test showed that patients with high expression of SPHK1 possessed shorter continuous disease-free survival time. Conclusively, SPHK1 may become a potential biomarker for sacral chordoma in predicting its recurrence and patients’ prognosis.
Literature
1.
go back to reference McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM. Chordoma: incidence and survival patterns in the United States, 1973-1995. Cancer Causes Control : CCC. 2001;12(1):1–11.PubMedCrossRef McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM. Chordoma: incidence and survival patterns in the United States, 1973-1995. Cancer Causes Control : CCC. 2001;12(1):1–11.PubMedCrossRef
5.
go back to reference Sciubba DM, Cheng JJ, Petteys RJ, Weber KL, Frassica DA, Gokaslan ZL. Chordoma of the sacrum and vertebral bodies. J Am Acad Orthop Surg. 2009;17(11):708–17.PubMed Sciubba DM, Cheng JJ, Petteys RJ, Weber KL, Frassica DA, Gokaslan ZL. Chordoma of the sacrum and vertebral bodies. J Am Acad Orthop Surg. 2009;17(11):708–17.PubMed
8.
go back to reference Guan H, Liu L, Cai J, Liu J, Ye C, Li M, et al. Sphingosine kinase 1 is overexpressed and promotes proliferation in human thyroid cancer. Mol Endocrinol (Baltimore, MD). 2011;25(11):1858-66. doi:10.1210/me.2011-1048. Guan H, Liu L, Cai J, Liu J, Ye C, Li M, et al. Sphingosine kinase 1 is overexpressed and promotes proliferation in human thyroid cancer. Mol Endocrinol (Baltimore, MD). 2011;25(11):1858-66. doi:10.​1210/​me.​2011-1048.
9.
go back to reference Malavaud B, Pchejetski D, Mazerolles C, de Paiva GR, Calvet C, Doumerc N, et al. Sphingosine kinase-1 activity and expression in human prostate cancer resection specimens. Eur J Cancer (Oxford, England: 1990). 2010;46(18):3417-24. doi:10.1016/j.ejca.2010.07.053. Malavaud B, Pchejetski D, Mazerolles C, de Paiva GR, Calvet C, Doumerc N, et al. Sphingosine kinase-1 activity and expression in human prostate cancer resection specimens. Eur J Cancer (Oxford, England: 1990). 2010;46(18):3417-24. doi:10.​1016/​j.​ejca.​2010.​07.​053.
11.
go back to reference Bektas M, Jolly PS, Muller C, Eberle J, Spiegel S, Geilen CC. Sphingosine kinase activity counteracts ceramide-mediated cell death in human melanoma cells: role of Bcl-2 expression. Oncogene. 2005;24(1):178–87. doi:10.1038/sj.onc.1208019.PubMedCrossRef Bektas M, Jolly PS, Muller C, Eberle J, Spiegel S, Geilen CC. Sphingosine kinase activity counteracts ceramide-mediated cell death in human melanoma cells: role of Bcl-2 expression. Oncogene. 2005;24(1):178–87. doi:10.​1038/​sj.​onc.​1208019.PubMedCrossRef
12.
13.
14.
go back to reference Liu SQ, Su YJ, Qin MB, Mao YB, Huang JA, Tang GD. Sphingosine kinase 1 promotes tumor progression and confers malignancy phenotypes of colon cancer by regulating the focal adhesion kinase pathway and adhesion molecules. Int J Oncol. 2013;42(2):617–26. doi:10.3892/ijo.2012.1733.PubMed Liu SQ, Su YJ, Qin MB, Mao YB, Huang JA, Tang GD. Sphingosine kinase 1 promotes tumor progression and confers malignancy phenotypes of colon cancer by regulating the focal adhesion kinase pathway and adhesion molecules. Int J Oncol. 2013;42(2):617–26. doi:10.​3892/​ijo.​2012.​1733.PubMed
15.
go back to reference Sabattini E, Bisgaard K, Ascani S, Poggi S, Piccioli M, Ceccarelli C, et al. The EnVision ++ system: a new immunohistochemical method for diagnostics and research. Critical comparison with the APAAP, ChemMate, CSA, LABC, and SABC techniques. J Clin Pathol. 1998;51(7):506–11.PubMedCrossRefPubMedCentral Sabattini E, Bisgaard K, Ascani S, Poggi S, Piccioli M, Ceccarelli C, et al. The EnVision ++ system: a new immunohistochemical method for diagnostics and research. Critical comparison with the APAAP, ChemMate, CSA, LABC, and SABC techniques. J Clin Pathol. 1998;51(7):506–11.PubMedCrossRefPubMedCentral
16.
go back to reference Yang H, Zhu L, Ebraheim NA, Liu X, Castillo S, Tang T, et al. Analysis of risk factors for recurrence after the resection of sacral chordoma combined with embolization. Spine J: Off J N Am Spine Soc. 2009;9(12):972–80. doi:10.1016/j.spinee.2009.08.447.CrossRef Yang H, Zhu L, Ebraheim NA, Liu X, Castillo S, Tang T, et al. Analysis of risk factors for recurrence after the resection of sacral chordoma combined with embolization. Spine J: Off J N Am Spine Soc. 2009;9(12):972–80. doi:10.​1016/​j.​spinee.​2009.​08.​447.CrossRef
17.
go back to reference Chen K, Mo J, Zhou M, Wang G, Wu G, Chen H, et al. Expression of PTEN and mTOR in sacral chordoma and association with poor prognosis. Med Oncol (Northwood, London, England). 2014;31(4):886. doi:10.1007/s12032-014-0886-7. Chen K, Mo J, Zhou M, Wang G, Wu G, Chen H, et al. Expression of PTEN and mTOR in sacral chordoma and association with poor prognosis. Med Oncol (Northwood, London, England). 2014;31(4):886. doi:10.​1007/​s12032-014-0886-7.
19.
go back to reference Chen KW, Yang HL, Lu J, Wang GL, Ji YM, Wu GZ, et al. Expression of vascular endothelial growth factor and matrix metalloproteinase-9 in sacral chordoma. J Neuro-Oncol. 2011;101(3):357–63. doi:10.1007/s11060-010-0263-0.CrossRef Chen KW, Yang HL, Lu J, Wang GL, Ji YM, Wu GZ, et al. Expression of vascular endothelial growth factor and matrix metalloproteinase-9 in sacral chordoma. J Neuro-Oncol. 2011;101(3):357–63. doi:10.​1007/​s11060-010-0263-0.CrossRef
20.
go back to reference Sukocheva O, Wang L, Verrier E, Vadas MA, Xia P. Restoring endocrine response in breast cancer cells by inhibition of the sphingosine kinase-1 signaling pathway. Endocrinology. 2009;150(10):4484–92. doi:10.1210/en.2009-0391.PubMedCrossRef Sukocheva O, Wang L, Verrier E, Vadas MA, Xia P. Restoring endocrine response in breast cancer cells by inhibition of the sphingosine kinase-1 signaling pathway. Endocrinology. 2009;150(10):4484–92. doi:10.​1210/​en.​2009-0391.PubMedCrossRef
21.
go back to reference Li W, Yu CP, Xia JT, Zhang L, Weng GX, Zheng HQ, et al. Sphingosine kinase 1 is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res: Off J Am Assoc Cancer Res. 2009;15(4):1393–9. doi:10.1158/1078-0432.ccr-08-1158.CrossRef Li W, Yu CP, Xia JT, Zhang L, Weng GX, Zheng HQ, et al. Sphingosine kinase 1 is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res: Off J Am Assoc Cancer Res. 2009;15(4):1393–9. doi:10.​1158/​1078-0432.​ccr-08-1158.CrossRef
23.
go back to reference Akhavan-Sigari R, Gaab MR, Rohde V, Abili M, Ostertag H. Expression of PDGFR-alpha, EGFR and c-MET in spinal chordoma: a series of 52 patients. Anticancer Res. 2014;34(2):623–30.PubMed Akhavan-Sigari R, Gaab MR, Rohde V, Abili M, Ostertag H. Expression of PDGFR-alpha, EGFR and c-MET in spinal chordoma: a series of 52 patients. Anticancer Res. 2014;34(2):623–30.PubMed
25.
go back to reference Sinha UK, Schorn VJ, Hochstim C, Chinn SB, Zhu S, Masood R. Increased radiation sensitivity of head and neck squamous cell carcinoma with sphingosine kinase 1 inhibition. Head Neck. 2011;33(2):178–88. doi:10.1002/hed.21418.PubMedCrossRef Sinha UK, Schorn VJ, Hochstim C, Chinn SB, Zhu S, Masood R. Increased radiation sensitivity of head and neck squamous cell carcinoma with sphingosine kinase 1 inhibition. Head Neck. 2011;33(2):178–88. doi:10.​1002/​hed.​21418.PubMedCrossRef
26.
go back to reference Watson C, Long JS, Orange C, Tannahill CL, Mallon E, McGlynn LM, et al. High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1, and extracellular signal-regulated kinase-1/2 is associated with development of tamoxifen resistance in estrogen receptor-positive breast cancer patients. Am J Pathol. 2010;177(5):2205–15. doi:10.2353/ajpath.2010.100220.PubMedCrossRefPubMedCentral Watson C, Long JS, Orange C, Tannahill CL, Mallon E, McGlynn LM, et al. High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1, and extracellular signal-regulated kinase-1/2 is associated with development of tamoxifen resistance in estrogen receptor-positive breast cancer patients. Am J Pathol. 2010;177(5):2205–15. doi:10.​2353/​ajpath.​2010.​100220.PubMedCrossRefPubMedCentral
27.
go back to reference Ohotski J, Long JS, Orange C, Elsberger B, Mallon E, Doughty J, et al. Expression of sphingosine 1-phosphate receptor 4 and sphingosine kinase 1 is associated with outcome in oestrogen receptor-negative breast cancer. Br J Cancer. 2012;106(8):1453–9. doi:10.1038/bjc.2012.98.PubMedCrossRefPubMedCentral Ohotski J, Long JS, Orange C, Elsberger B, Mallon E, Doughty J, et al. Expression of sphingosine 1-phosphate receptor 4 and sphingosine kinase 1 is associated with outcome in oestrogen receptor-negative breast cancer. Br J Cancer. 2012;106(8):1453–9. doi:10.​1038/​bjc.​2012.​98.PubMedCrossRefPubMedCentral
28.
go back to reference Song L, Xiong H, Li J, Liao W, Wang L, Wu J, et al. Sphingosine kinase-1 enhances resistance to apoptosis through activation of PI3 K/Akt/NF-kappaB pathway in human non-small cell lung cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2011;17(7):1839–49. doi:10.1158/1078-0432.ccr-10-0720.CrossRef Song L, Xiong H, Li J, Liao W, Wang L, Wu J, et al. Sphingosine kinase-1 enhances resistance to apoptosis through activation of PI3 K/Akt/NF-kappaB pathway in human non-small cell lung cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2011;17(7):1839–49. doi:10.​1158/​1078-0432.​ccr-10-0720.CrossRef
Metadata
Title
High expression of SPHK1 in sacral chordoma and association with patients’ poor prognosis
Authors
Kai Zhang
Hao Chen
Guizhong Wu
Kangwu Chen
Huilin Yang
Publication date
01-11-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 11/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0247-6

Other articles of this Issue 11/2014

Medical Oncology 11/2014 Go to the issue