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.
Similar content being viewed by others
References
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.
Maclean FM, Soo MY, Ng T. Chordoma: radiological-pathological correlation. Australas Radiol. 2005;49(4):261–8. doi:10.1111/j.1440-1673.2005.01433.x.
Casali PG, Stacchiotti S, Sangalli C, Olmi P, Gronchi A. Chordoma. Curr Opin Oncol. 2007;19(4):367–70. doi:10.1097/CCO.0b013e3281214448.
Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH. Chordoma: the nonsarcoma primary bone tumor. Oncologist. 2007;12(11):1344–50. doi:10.1634/theoncologist.12-11-1344.
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.
Hanna SA, Aston WJ, Briggs TW, Cannon SR, Saifuddin A. Sacral chordoma: can local recurrence after sacrectomy be predicted? Clin Orthop Relat Res. 2008;466(9):2217–23. doi:10.1007/s11999-008-0356-7.
Knapp P, Baranowski M, Knapp M, Zabielski P, Blachnio-Zabielska AU, Gorski J. Altered sphingolipid metabolism in human endometrial cancer. Prostaglandins Other Lipid Mediat. 2010;92(1–4):62–6. doi:10.1016/j.prostaglandins.2010.03.002.
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.
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.
Facchinetti MM, Gandini NA, Fermento ME, Sterin-Speziale NB, Ji Y, Patel V, et al. The expression of sphingosine kinase-1 in head and neck carcinoma. Cells Tissues Organs. 2010;192(5):314–24. doi:10.1159/000318173.
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.
Bao M, Chen Z, Xu Y, Zhao Y, Zha R, Huang S, et al. Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P/EDG1 axis in hepatocellular carcinoma. Liver Int: Off J Int Assoc Study Liver. 2012;32(2):331–8. doi:10.1111/j.1478-3231.2011.02666.x.
Shida D, Takabe K, Kapitonov D, Milstien S, Spiegel S. Targeting SphK1 as a new strategy against cancer. Curr Drug Targets. 2008;9(8):662–73.
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.
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.
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.
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 KW, Yang HL, Lu J, Liu JY, Chen XQ. Prognostic factors of sacral chordoma after surgical therapy: a study of 36 patients. Spinal Cord. 2010;48(2):166–71. doi:10.1038/sc.2009.95.
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.
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.
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.
Pan J, Tao YF, Zhou Z, Cao BR, Wu SY, Zhang YL, et al. An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma. J Transl Med. 2011;9:157. doi:10.1186/1479-5876-9-157.
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.
Shida D, Kitayama J, Yamaguchi H, Yamashita H, Mori K, Watanabe T, et al. Sphingosine 1-phosphate transactivates c-Met as well as epidermal growth factor receptor (EGFR) in human gastric cancer cells. FEBS Lett. 2004;577(3):333–8. doi:10.1016/j.febslet.2004.10.024.
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.
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.
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.
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.
Acknowledgments
We would like to thank Gu Yongping for technical guidance during the immunohistochemical analysis.
Conflict of interest
None.
Ethical standard
Our study was approved by the Committee on Medical Ethics of the First affiliated Hospital of Soochow University.
Author information
Authors and Affiliations
Corresponding authors
Additional information
K. Zhang and H. Chen have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Zhang, K., Chen, H., Wu, G. et al. High expression of SPHK1 in sacral chordoma and association with patients’ poor prognosis. Med Oncol 31, 247 (2014). https://doi.org/10.1007/s12032-014-0247-6
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12032-014-0247-6