Overexpression of sphingosine kinase 1 is associated with salivary gland carcinoma progression and might be a novel predictive marker for adjuvant therapy

Abstract

BackgroundOverexpression of sphingosine kinase-1 (SPHK1) has been demonstrated to be associated with the development and progression in various types of human cancers. The current study was to characterize the expression of SPHK1 in salivary gland carcinomas (SGC) and to investigate the association between SPHK1 expression and progression of SGC.MethodsThe expression of SPHK1 was examined in 2 normal salivary gland tissues, 8 SGC tissues of various clinical stages, and 5 pairs of primary SGC and adjacent salivary gland tissues from the same patient, using real-time PCR and western blot analysis. Furthermore, the SPHK1 protein expression was analyzed in 159 clinicopathologically characterized SGC cases by immunohistochemistry. Statistical analyses were performed to determine the prognostic and diagnostic associations.ResultsSPHK1 expression was found to be markedly upregulated in SGC tissues than that in the normal salivary gland tissues and paired adjacent salivary gland tissues, at both mRNA and protein levels. Statistical analysis revealed a significant correlation of SPHK1 expression with the clinical stage (P = 0.005), T classification (P = 0.017), N classification (P = 0.009), M classification (P = 0.002), and pathological differentiation (P = 0.013). Patients with higher SPHK1 expression had shorter overall survival time, whereas patients with lower SPHK1 expression had better survival. Importantly, patients in the group without adjuvant therapy who exhibited high SPHK1 expression had significantly lower overall survival rates compared with those with low SPHK1 expression. Moreover, multivariate analysis suggested that SPHK1 expression might be an independent prognostic indicator for the survival of SGC patients.ConclusionsOur results suggest that SPHK1 expression is associated with SGC progression, and might represent as a novel and valuable predictor for adjuvant therapy to SGC patients.

Predictive Value of Sphingosine Kinase 1 Expression in Papillary Thyroid Carcinoma

“…Sphingosine kinase 1 expression was significantly increased in thyroid cancer tissues compared to nodular goiter (p<0.001) and normal thyroid (p<0.001) tissues, consistent with previous results (14,16,20,(32)(33)(34). We observed that 34 (30.9%) of 110 papillary thyroid carcinoma tissue samples had high sphingosine kinase 1 expression.…”

C6-Ceramide and targeted inhibition of acid ceramidase induce synergistic decreases in breast cancer cell growth

“…This is supported by reports of dysregulation of ceramide metabolizing enzymes in a variety of human tumors and tumor cell types [6,[8][9][10][11][12][13][14]. Thus, targeting the ceramide pathway has gained considerable interest as a means of improving response to anti-cancer therapies [54].…”

“…Ceramide metabolism is known to play a role in development of the multidrug resistant phenotype [4][5][6][7], as is evidenced by the reported dysregulation of ceramide metabolizing enzymes in a variety of tumor types [6,[8][9][10][11][12][13][14][15].…”

Sphingosine Kinase 1 Is Overexpressed and Promotes Proliferation in Human Thyroid Cancer

“…It has been well documented that the expression of SphK1 is elevated in various types of human cancers, including glioma, head and neck squamous cell carcinoma, prostate cancer, salivary gland carcinoma, gastric cancer, and non-Hodgkin lymphomas (9 -14). Intriguingly, the increased expression of SphK1 among some of these cancers has been associated with worse clinical outcome of patients (11)(12)(13). In vitro tumor growth was pronouncedly reduced when the cellular SphK1 activity was abolished via pharmacological and genetic inhibition (15,16).…”