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.
Highlights
Overexpression of sphingosine kinase-1 (SPHK1) has been demonstrated to be associated with the development and progression in various types of human cancers
Expression of SPHK1 is upregulated in salivary gland carcinomas (SGC) To investigate whether SPHK1 expression is upregulated in clinical SGC tissues, real-time PCR analysis and western blot analysis were performed in 2 normal salivary gland tissues and 8 fresh-frozen SGC tissues
In parallel with the upregulation of mRNA, western blot analysis revealed that SPHK1 protein was overexpressed in all 8 SGC, whereas it was barely detectable in normal salivary gland tissues (Fig. 1B)
Summary
Overexpression of sphingosine kinase-1 (SPHK1) has been demonstrated to be associated with the development and progression in various types of human cancers. Salivary gland carcinoma (SGC), a relatively rare neoplasm, accounts for 0.5% of all malignancies and approximately 3%-5% of all head and neck cancers worldwide [1,2]. More than 5% of patients suffered a recurrence at the primary site and/or distant metastases, the latter of which are not amenable to surgery or radiotherapy [5]. It will be of great clinical value to identify effective early markers for the diagnosis and prognosis of the disease and novel therapeutic targets
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