| Journal of Translational Medicine | |
| Secreted protein acidic and rich in cysteine (SPARC) is associated with nasopharyngeal carcinoma metastasis and poor prognosis | |
| Jian-Yong Shao2  Yi-Xin Zeng2  Man-Bo Cai2  Fang Wang3  Jing-Hui Hou1  Qiong Shao3  Yang-Yang Li3  Hai-Yun Wang3  | |
| [1] Department of Pathology, Sun Yat-Sen University Cancer Center, 651 Dong Feng Road East, Guangzhou 510060, People's Republic of China;Department of Experiment Research, Sun Yat-Sen University Cancer Center, 651 Dong Feng Road East, Guangzhou 510060, People's Republic of China;Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, 651 Dong Feng Road East, Guangzhou 510060, People's Republic of China | |
| 关键词: Metastasis; Nasopharyngeal carcinoma; SPARC; | |
| Others : 1206054 DOI : 10.1186/1479-5876-10-27 |
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| received in 2011-08-22, accepted in 2012-02-09, 发布年份 2012 | |
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【 摘 要 】
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.
【 授权许可】
2012 Wang et al; licensee BioMed Central Ltd.
【 预 览 】
| Files | Size | Format | View |
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| 20150526120332102.pdf | 1864KB | ||
| Figure 3. | 57KB | Image | |
| Figure 2. | 193KB | Image | |
| Figure 1. | 39KB | Image |
【 图 表 】
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【 参考文献 】
- [1]Hsu MM, Tu SM: Nasopharyngeal carcinoma in Taiwan. Clinical manifestations and results of therapy. Cancer 1983, 52:362-368.
- [2]Vokes EE, Liebowitz DN, Weichselbaum RR: Nasopharyngeal carcinoma. Lancet 1997, 350:1087-1091.
- [3]Cvitkovic E, Bachouchi M, Boussen H, Busson P, Rousselet G, Mahjoubi R, Flores P, Tursz T, Armand JP, Azli N: Leukemoid reaction, bone marrow invasion, fever of unknown origin, and metastatic pattern in the natural history of advanced undifferentiated carcinoma of nasopharyngeal type: a review of 255 consecutive cases. J Clin Oncol 1993, 11:2434-2442.
- [4]Ahmad A, Stefani S: Distant metastases of nasopharyngeal carcinoma: a study of 256 male patients. J Surg Oncol 1986, 33:194-197.
- [5]Chan AS, To KF, Lo KW, Mak KF, Pak W, Chiu B, Tse GM, Ding M, Li X, Lee JC, Huang DP: High frequency of chromosome 3p deletion in histologically normal nasopharyngeal epithelia from southern Chinese. Cancer Res 2000, 60:5365-5370.
- [6]Hong MH, Mai HQ, Min HQ, Ma J, Zhang EP, Cui NJ: A comparison of the Chinese 1992 and fifth-edition International Union Against Cancer staging systems for staging nasopharyngeal carcinoma. Cancer 2000, 89:242-247.
- [7]Heng DM, Wee J, Fong KW, Lian LG, Sethi VK, Chua ET, Yang TL, Khoo-Tan HS, Lee KS, Lee KM, et al.: Prognostic factors in 677 patients in Singapore with nondisseminated nasopharyngeal carcinoma. Cancer 1999, 86:1912-1920.
- [8]Baranska B, Kujawa M, Szulborski K: Formation of the nemaline structures in soleus muscle of rats subjected to long-lasting immobilization. Folia Morphol (Warsz) 1999, 58:207-214.
- [9]Tatsumi-Tamori A, Yoshizaki T, Miwa T, Furukawa M: Clinical evaluation of staging system for nasopharyngeal carcinoma: comparison of fourth and fifth editions of UICC TNM classification. Ann Otol Rhinol Laryngol 2000, 109:1125-1129.
- [10]Rhee DJ, Haddadin RI, Kang MH, Oh DJ: Matricellular proteins in the trabecular meshwork. Exp Eye Res 2009, 88:694-703.
- [11]Maillard C, Malaval L, Delmas PD: Immunological screening of SPARC/Osteonectin in nonmineralized tissues. Bone 1992, 13:257-264.
- [12]Porter PL, Sage EH, Lane TF, Funk SE, Gown AM: Distribution of SPARC in normal and neoplastic human tissue. J Histochem Cytochem 1995, 43:791-800.
- [13]Wang CS, Lin KH, Chen SL, Chan YF, Hsueh S: Overexpression of SPARC gene in human gastric carcinoma and its clinic-pathologic significance. Br J Cancer 2004, 91:1924-1930.
- [14]Zhao ZS, Wang YY, Chu YQ, Ye ZY, Tao HQ: SPARC is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res 2010, 16:260-268.
- [15]Bergamaschi A, Tagliabue E, Sorlie T, Naume B, Triulzi T, Orlandi R, Russnes HG, Nesland JM, Tammi R, Auvinen P, et al.: Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol 2008, 214:357-367.
- [16]Helleman J, Jansen MP, Ruigrok-Ritstier K, van Staveren IL, Look MP, Meijer-van-Gelder ME, Sieuwerts AM, Klijn JG, Sleijfer S, Foekens JA, Berns EM: Association of an extracellular matrix gene cluster with breast cancer prognosis and endocrine therapy response. Clin Cancer Res 2008, 14:5555-5564.
- [17]Watkins G, Douglas-Jones A, Bryce R, Mansel RE, Jiang WG: Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes. Prostaglandins Leukot Essent Fatty Acids 2005, 72:267-272.
- [18]Dalla-Torre CA, Yoshimoto M, Lee CH, Joshua AM, de Toledo SR, Petrilli AS, Andrade JA, Chilton-MacNeill S, Zielenska M, Squire JA: Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma. BMC Cancer 2006, 6:237. BioMed Central Full Text
- [19]Rich JN, Hans C, Jones B, Iversen ES, McLendon RE, Rasheed BK, Dobra A, Dressman HK, Bigner DD, Nevins JR, West M: Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res 2005, 65:4051-4058.
- [20]Yamashita K, Upadhay S, Mimori K, Inoue H, Mori M: Clinical significance of secreted protein acidic and rich in cystein in esophageal carcinoma and its relation to carcinoma progression. Cancer 2003, 97:2412-2419.
- [21]Yamanaka M, Kanda K, Li NC, Fukumori T, Oka N, Kanayama HO, Kagawa S: Analysis of the gene expression of SPARC and its prognostic value for bladder cancer. J Urol 2001, 166:2495-2499.
- [22]Bozkurt SU, Ayan E, Bolukbasi F, Elmaci I, Pamir N, Sav A: Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomas. APMIS 2009, 117:651-659.
- [23]Kato Y, Nagashima Y, Baba Y, Kawano T, Furukawa M, Kubota A, Yanoma S, Imagawa-Ishiguro Y, Satake K, Taguchi T, et al.: Expression of SPARC in tongue carcinoma of stage II is associated with poor prognosis: an immunohistochemical study of 86 cases. Int J Mol Med 2005, 16:263-268.
- [24]Chin D, Boyle GM, Williams RM, Ferguson K, Pandeya N, Pedley J, Campbell CM, Theile DR, Parsons PG, Coman WB: Novel markers for poor prognosis in head and neck cancer. Int J Cancer 2005, 113:789-797.
- [25]Massi D, Franchi A, Borgognoni L, Reali UM, Santucci M: Osteonectin expression correlates with clinical outcome in thin cutaneous malignant melanomas. Hum Pathol 1999, 30:339-344.
- [26]Infante JR, Matsubayashi H, Sato N, Tonascia J, Klein AP, Riall TA, Yeo C, Iacobuzio-Donahue C, Goggins M: Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol 2007, 25:319-325.
- [27]Mantoni TS, Schendel RR, Rodel F, Niedobitek G, Al-Assar O, Masamune A, Brunner TB: Stromal SPARC expression and patient survival after chemoradiation for non-resectable pancreatic adenocarcinoma. Cancer Biol Ther 2008, 7:1806-1815.
- [28]Koukourakis MI, Giatromanolaki A, Brekken RA, Sivridis E, Gatter KC, Harris AL, Sage EH: Enhanced expression of SPARC/osteonectin in the tumor-associated stroma of non-small cell lung cancer is correlated with markers of hypoxia/acidity and with poor prognosis of patients. Cancer Res 2003, 63:5376-5380.
- [29]Min H, Hong M, Ma J, Zhang E, Zheng Q, Zhang J, Zhang F, Su Y, Qiu F: A new staging system for nasopharyngeal carcinoma in China. Int J Radiat Oncol Biol Phys 1994, 30:1037-1042.
- [30]Chua DT, Sham JS, Wei WI, Ho WK, Au GK: The predictive value of the 1997 American Joint Committee on Cancer stage classification in determining failure patterns in nasopharyngeal carcinoma. Cancer 2001, 92:2845-2855.
- [31]Wang HY, Sun BY, Zhu ZH, Chang ET, To KF, Hwang JS, Jiang H, Kam MK, Chen G, Cheah SL, et al.: Eight-signature classifier for prediction of nasopharnyngeal carcinoma survival. J Clin Oncol 2011, 29:4516-4525.
- [32]Chen J, Hu CF, Hou JH, Shao Q, Yan LX, Zhu XF, Zeng YX, Shao JY: Epstein-Barr virus encoded latent membrane protein 1 regulates mTOR signaling pathway genes which predict poor prognosis of nasopharyngeal carcinoma. J Transl Med 2010, 8:30. BioMed Central Full Text
- [33]Song LB, Zeng MS, Liao WT, Zhang L, Mo HY, Liu WL, Shao JY, Wu QL, Li MZ, Xia YF, et al.: Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. Cancer Res 2006, 66:6225-6232.
- [34]Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX, Shao JY: MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 2008, 14:2348-2360.
- [35]Sakai N, Baba M, Nagasima Y, Kato Y, Hirai K, Kondo K, Kobayashi K, Yoshida M, Kaneko S, Kishida T, et al.: SPARC expression in primary human renal cell carcinoma: upregulation of SPARC in sarcomatoid renal carcinoma. Hum Pathol 2001, 32:1064-1070.
- [36]Takano T, Hasegawa Y, Matsuzuka F, Miyauchi A, Yoshida H, Higashiyama T, Kuma K, Amino N: Gene expression profiles in thyroid carcinomas. Br J Cancer 2000, 83:1495-1502.
- [37]Menon PM, Gutierrez JA, Rempel SA: A study of SPARC and vitronectin localization and expression in pediatric and adult gliomas: high SPARC secretion correlates with decreased migration on vitronectin. Int J Oncol 2000, 17:683-693.
- [38]Le Bail B, Faouzi S, Boussarie L, Guirouilh J, Blanc JF, Carles J, Bioulac-Sage P, Balabaud C, Rosenbaum J: Osteonectin/SPARC is overexpressed in human hepatocellular carcinoma. J Pathol 1999, 189:46-52.
- [39]O'Sullivan B: Nasopharynx cancer: therapeutic value of chemoradiotherapy. Int J Radiat Oncol Biol Phys 2007, 69:S118-S121.
- [40]Wei WI, Sham JS: Nasopharyngeal carcinoma. Lancet 2005, 365:2041-2054.
- [41]Razak AR, Siu LL, Liu FF, Ito E, O'Sullivan B, Chan K: Nasopharyngeal carcinoma: the next challenges. Eur J Cancer 2010, 46:1967-1978.
- [42]Chien YC, Chen JY, Liu MY, Yang HI, Hsu MM, Chen CJ, Yang CS: Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med 2001, 345:1877-1882.
- [43]Greenwood JA, Murphy-Ullrich JE: Signaling of de-adhesion in cellular regulation and motility. Microsc Res Tech 1998, 43:420-432.
- [44]Tai IT, Tang MJ: SPARC in cancer biology: its role in cancer progression and potential for therapy. Drug Resist Updat 2008, 11:231-246.
- [45]Huang DY, Lin YT, Jan PS, Hwang YC, Liang ST, Peng Y, Huang CY, Wu HC, Lin CT: Transcription factor SOX-5 enhances nasopharyngeal carcinoma progression by down-regulating SPARC gene expression. J Pathol 2008, 214:445-455.
- [46]Framson PE, Sage EH: SPARC and tumor growth: where the seed meets the soil? J Cell Biochem 2004, 92:679-690.
- [47]Podhajcer OL, Benedetti LG, Girotti MR, Prada F, Salvatierra E, Llera AS: The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host. Cancer Metastasis Rev 2008, 27:691-705.
- [48]Clark CJ, Sage EH: A prototypic matricellular protein in the tumor microenvironment-where there's SPARC, there's fire. J Cell Biochem 2008, 104:721-732.
- [49]Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, et al.: Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA 2004, 101:811-816.
- [50]Thomas R, True LD, Bassuk JA, Lange PH, Vessella RL: Differential expression of osteonectin/SPARC during human prostate cancer progression. Clin Cancer Res 2000, 6:1140-1149.
- [51]Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, Kurachi K, Pienta KJ, Rubin MA, Chinnaiyan AM: Delineation of prognostic biomarkers in prostate cancer. Nature 2001, 412:822-826.
- [52]Kunigal S, Gondi CS, Gujrati M, Lakka SS, Dinh DH, Olivero WC, Rao JS: SPARC-induced migration of glioblastoma cell lines via uPA-uPAR signaling and activation of small GTPase RhoA. Int J Oncol 2006, 29:1349-1357.
- [53]Kong QL, Guan S, Guo BH, Zeng MS: Pre-malignant nasopharyngeal epithelial cell models. Ai Zheng 2009, 28:1012-1015.
- [54]Chlenski A, Liu S, Crawford SE, Volpert OV, DeVries GH, Evangelista A, Yang Q, Salwen HR, Farrer R, Bray J, Cohn SL: SPARC is a key Schwannian-derived inhibitor controlling neuroblastoma tumor angiogenesis. Cancer Res 2002, 62:7357-7363.
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