Abstract
BackgroundThe aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC) in nasopharyngeal carcinoma (NPC) specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPCMethodsNPC tissue microarrays (TMAs) were constructed from Sun Yat-sen University Cancer Center (SYSUCC), another three centers on mainland China, Singapore and Hong Kong. Using quantitative RT-PCR and Western-blotting techniques, we detected mRNA and protein expression of SPARC in NPC cell lines and immortalized nasopharyngeal epithelial cells (NPECs) induced by Bmi-1 (NPEC2 Bmi-1). The difference of SPARC expression in the cell lines was tested using a t-test method. The relationship between the SPARC expression and clinicopathological data was assessed by chi-square. Survival analysis was estimated using the Kaplan-Meier approach with log-rank test. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models.ResultsThe expression levels of SPARC mRNA and protein were markedly higher in NPC cell lines than in NPEC2 Bmi-1. Especially, the expression levels of SPARC mRNA and protein were much lower in the 6-10B than in the 5-8 F (P = 0.002, P = 0.001). SPARC immunostaining revealed cytoplasmic localization in NPC cells and no staining in the stroma and epithelium.In addition, high level of SPARC positively correlated with the status of distant metastasis (P = 0.001) and WHO histological classification (P = 0.023). NPC patients with high SPARC expression also had a significantly poorer prognosis than patients with low SPARC expression (log-rank test, P < 0.001), especially patients with advanced stage disease (log-rank, P < 0.001). Multivariate analysis suggested that the level of SPARC expression was an independent prognostic indicator for the overall survival of patients with NPC (P < 0.001).ConclusionsSPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC.
Highlights
The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC) in nasopharyngeal carcinoma (NPC) specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC
SPARC expression in NPC cell lines and tissue We first evaluated the endogenous expression of SPARC in several human NPC cell lines and NPEC2 Bmi-1 cell line
Compared to NPEC2 Bmi-1 cells, high expression levels of SPARC mRNA were observed in the NPC cell lines CNE1, CNE2, HONE1, SUNE1 and C666 (Figure 1A)
Summary
The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC) in nasopharyngeal carcinoma (NPC) specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC. Nasopharyngeal carcinoma (NPC) is unique amongst head and neck cancers because of its peculiar epidemiological and biological characteristics. Unlike other head and neck malignancies, NPC is notorious for its highly metastatic nature [1]. NPC is classified as a subtype of head and neck squamous cell carcinoma, its unique epidemiology, clinical characteristics, etiology, and histopathology warrant separate efforts for the study of its underlying molecular mechanisms of carcinogenesis [2]. NPC patients tend to present at a more advanced stage of disease because the primary anatomical site of tumor growth is located in a silent area, and they exhibit higher metastatic potential when compared to other head and neck squamous cell carcinoma [3,4,5]
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