Expression Of SPHK1 In Sacral Chordoma And Association With MAPK Pathway

PartⅠ Expression of SPHK1 in sacral chordoma and association withpatients’ prognosisPurpose: 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. The purpose of our research was to evaluate the expression of SPHK1 in sacral chordoma and its clinical significance, so as to provide evidences for tumor prognosis and molecular target therapy.Methods: In this study, we detected the expression of sphingosine kinase 1(SPHK1) in 42 sacral chordoma samples and 16 distant normal tissue specimens by immunohistochemical staining and q RT-PCR. In addition, we analyzed its association with the clinical factors and patients’ prognosis.Results: Immunohistochemical staining results revealed that 69%(29/42) of all the 42 chordoma samples showed high expression of SPHK1, whereas, only 19%(3/16) of distant normal tissues expressed a high level of SPHK1(P=0.001). Meantime, q RT-PCR results also showed that SPHK1 m RNA was significantly higher in sacral chordoma than in distant normal tissue(P<0.05). Chi-Square analysis revealed that high expression of SPHK1 was significantly correlated with tumor recurrence(P=0.019) and invasion into surrounding normal tissue(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(CDFS).Conclusion: SPHK1 m RNA and protein expression was significantly evaluated in sacral chordoma,it was closely related to tumor invasion and recurrence, which might become a potential biomarker and therapy target for sacral chordoma.PartⅡ The expression of SPHK1 in sacral chordoma and associationwith MAPK pathwayPurpose: Chordoma is a rare and low-malignant neoplasm which is considered to arise from notochord remnants. It has been reported that SPHK1 can enhance the tumor development by regulating MAPK pathway. Mitogen-activated protein kinase signaling pathway is acknowledged to participate in tumor development, in which RAF-1 and extracellular regulated protein kinase 1/2(ERK1/2) play vital roles. In this study, we aimed to detect the association of SPHK1 expression with MAPK pathway.Methods: We evaluated the expression of SPHK1 、 RAF-1 and ERK1/2 by immunohistochemical staining in 42 chordoma tissue and 16 distant normal tissue. Moreover, we also investigated the correlations of RAF-1 and ERK1/2 expression with SPHK1 and clinical features in sacral chordoma.Results: Expression of RAF-1 and ERK1/2 was both significantly higher in sacral chordoma tissue than distant normal tissue(P=0.008, P=0.019). Spearman correlation test showed expression of SPHK1 was significantly related to RAF-1 and ERK1/2 expression(P=0.016, P=0.011).Meanwhile, RAF-1 has close relation to ERK1/2 expression(P=0.001).Chi-Square analysis and t test revealed that RAF-1 positive expression was related to surrounding muscle invasion(P=0.032) and chordoma recurrence(P=0.002), but the results did not indicate any association with patients’ age, gender, tumor size and location. ERK1/2 was associated with tumor size(P=0.044) instead of other clinical factors(P>0.05). Kaplan–Meier survival Curve and log-rank test showed that RAF-1 positive expression was associated with shorter continuous disease-free survival time(CDFS)(P<0.005), while ERK1/2 had no relation to CDFS(P=0.961).Conclusions: Expression of RAF-1 and ERK1/2 in sacral chordoma was up-regulated, which was significantly related to expression of SPHK1. SPHK1 may promote the invasion and recurrence of sacral chordoma by regulating MAPK pathway.