Secreted protein acidic and rich in cysteine (SPARC) is associated with nasopharyngeal carcinoma metastasis and poor prognosis.
BACKGROUND
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.


METHODS
NPC 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.


RESULTS
The 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).


CONCLUSIONS
SPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC.
State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Hai-Yun
HY
Wang
Yang-Yang
YY
Li
Qiong
Q
Shao
Jing-Hui
JH
Hou
Fang
F
Wang
Man-Bo
MB
Cai
Yi-Xin
YX
Zeng
Jian-Yong
JY
Shao
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D045744:Cell Line, Tumor; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D009362:Neoplasm Metastasis; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D015676:Osteonectin