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Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

Nuclear overexpression of metastasis-associated protein 1 correlates significantly with poor survival in nasopharyngeal carcinoma

Authors: Wen-Fei Li, Na Liu, Rui-Xue Cui, Qing-Mei He, Mo Chen, Ning Jiang, Ying Sun, Jing Zeng, Li-Zhi Liu, Jun Ma

Published in: Journal of Translational Medicine | Issue 1/2012

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Abstract

Background

Metastasis-associated protein 1 (MTA1) has been associated with poor prognosis in several malignant carcinomas. The purpose of this study was to investigate the expression and prognostic value of MTA1 in nasopharyngeal carcinoma (NPC).

Methods

MTA1 expression was assessed using immunohistochemistry in paraffin-embedded tumor specimens from 208 untreated NPC patients. Cox regression analysis was used to calculate the hazard ratio (HR), 95% confidence interval (CI) and identify independent prognostic factors, and recursive partitioning analysis was used to create a decision tree.

Results

Nuclear overexpression of MTA1 was observed in 48.6% (101/208) of the NPC tissues. Nuclear overexpression of MTA1 correlated positively with N classification (P = 0.02), clinical stage (P = 0.04), distant metastasis (P < 0.01) and death (P = 0.01). Additionally, nuclear overexpression of MTA1 correlated significantly with poorer distant metastasis-free survival (DMFS; P <0.01) and poorer overall survival (OS; P < 0.01). MTA1 had prognostic significance in NPC patients with stage II disease, but not stage III or IV disease. Multivariate analysis demonstrated that nuclear overexpression of MTA1 was independently associated with poorer DMFS (HR, 2.05; 95% CI, 1.13–3.72; P = 0.02) and poorer OS (HR, 1.98; 95% CI, 1.09–3.59; P = 0.03). Using recursive partitioning analysis, the NPC patients could be classified with a low, intermediate or high risk of distant metastasis and death, on the basis of clinical stage, age and MTA1 expression.

Conclusion

The results of this study suggest that nuclear overexpression of MTA1 correlates significantly with poorer DMFS and poorer OS in NPC. MTA1 has potential as a novel prognostic biomarker in NPC.
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Literature
2.
go back to reference Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ, Ma J: How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?. Int J Radiat Oncol Biol Phys. 2011, 80: 661-668. 10.1016/j.ijrobp.2010.03.024.CrossRefPubMed Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ, Ma J: How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?. Int J Radiat Oncol Biol Phys. 2011, 80: 661-668. 10.1016/j.ijrobp.2010.03.024.CrossRefPubMed
4.
go back to reference Kumar R, Wang RA, Bagheri-Yarmand R: Emerging roles of MTA family members in human cancers. Semin Oncol. 2003, 30: 30-37.CrossRefPubMed Kumar R, Wang RA, Bagheri-Yarmand R: Emerging roles of MTA family members in human cancers. Semin Oncol. 2003, 30: 30-37.CrossRefPubMed
5.
go back to reference Toh Y, Nicolson GL: The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clin Exp Metastasis. 2009, 26: 215-227. 10.1007/s10585-008-9233-8.CrossRefPubMed Toh Y, Nicolson GL: The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clin Exp Metastasis. 2009, 26: 215-227. 10.1007/s10585-008-9233-8.CrossRefPubMed
6.
go back to reference Xue Y, Wong J, Moreno GT, Young MK, Cote J, Wang W: NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell. 1998, 2: 851-861. 10.1016/S1097-2765(00)80299-3.CrossRefPubMed Xue Y, Wong J, Moreno GT, Young MK, Cote J, Wang W: NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell. 1998, 2: 851-861. 10.1016/S1097-2765(00)80299-3.CrossRefPubMed
7.
go back to reference Bowen NJ, Fujita N, Kajita M, Wade PA: Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta. 2004, 1677: 52-57. 10.1016/j.bbaexp.2003.10.010.CrossRefPubMed Bowen NJ, Fujita N, Kajita M, Wade PA: Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta. 2004, 1677: 52-57. 10.1016/j.bbaexp.2003.10.010.CrossRefPubMed
8.
go back to reference Toh Y, Pencil SD, Nicolson GL: A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. J Biol Chem. 1994, 269: 22958-22963.PubMed Toh Y, Pencil SD, Nicolson GL: A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. J Biol Chem. 1994, 269: 22958-22963.PubMed
9.
go back to reference Nawa A, Nishimori K, Lin P, Maki Y, Moue K, Sawada H, Toh Y, Fumitaka K, Nicolson GL: Tumor metastasis-associated human MTA1 gene: its deduced protein sequence, localization, and association with breast cancer cell proliferation using antisense phosphorothioate oligonucleotides. J Cell Biochem. 2000, 79: 202-212. 10.1002/1097-4644(20001101)79:2<202::AID-JCB40>3.0.CO;2-L.CrossRefPubMed Nawa A, Nishimori K, Lin P, Maki Y, Moue K, Sawada H, Toh Y, Fumitaka K, Nicolson GL: Tumor metastasis-associated human MTA1 gene: its deduced protein sequence, localization, and association with breast cancer cell proliferation using antisense phosphorothioate oligonucleotides. J Cell Biochem. 2000, 79: 202-212. 10.1002/1097-4644(20001101)79:2<202::AID-JCB40>3.0.CO;2-L.CrossRefPubMed
10.
go back to reference Nicolson GL, Nawa A, Toh Y, Taniguchi S, Nishimori K, Moustafa A: Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clin Exp Metastasis. 2003, 20: 19-24. 10.1023/A:1022534217769.CrossRefPubMed Nicolson GL, Nawa A, Toh Y, Taniguchi S, Nishimori K, Moustafa A: Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clin Exp Metastasis. 2003, 20: 19-24. 10.1023/A:1022534217769.CrossRefPubMed
11.
go back to reference Toh Y, Oki E, Oda S, Tokunaga E, Ohno S, Maehara Y, Nicolson GL, Sugimachi K: Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis. Int J Cancer. 1997, 74: 459-463. 10.1002/(SICI)1097-0215(19970822)74:4<459::AID-IJC18>3.0.CO;2-4.CrossRefPubMed Toh Y, Oki E, Oda S, Tokunaga E, Ohno S, Maehara Y, Nicolson GL, Sugimachi K: Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis. Int J Cancer. 1997, 74: 459-463. 10.1002/(SICI)1097-0215(19970822)74:4<459::AID-IJC18>3.0.CO;2-4.CrossRefPubMed
12.
go back to reference Toh Y, Kuwano H, Mori M, Nicolson GL, Sugimachi K: Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas. Br J Cancer. 1999, 79: 1723-1726. 10.1038/sj.bjc.6690274.CrossRefPubMedPubMedCentral Toh Y, Kuwano H, Mori M, Nicolson GL, Sugimachi K: Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas. Br J Cancer. 1999, 79: 1723-1726. 10.1038/sj.bjc.6690274.CrossRefPubMedPubMedCentral
13.
go back to reference Hofer MD, Kuefer R, Varambally S, Li H, Ma J, Shapiro GI, Gschwend JE, Hautmann RE, Sanda MG, Giehl K: The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res. 2004, 64: 825-829. 10.1158/0008-5472.CAN-03-2755.CrossRefPubMed Hofer MD, Kuefer R, Varambally S, Li H, Ma J, Shapiro GI, Gschwend JE, Hautmann RE, Sanda MG, Giehl K: The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res. 2004, 64: 825-829. 10.1158/0008-5472.CAN-03-2755.CrossRefPubMed
14.
go back to reference Martin MD, Hilsenbeck SG, Mohsin SK, Hopp TA, Clark GM, Osborne CK, Allred DC, O’Connell P: Breast tumors that overexpress nuclear metastasis-associated 1 (MTA1) protein have high recurrence risks but enhanced responses to systemic therapies. Breast Cancer Res Treat. 2006, 95: 7-12. 10.1007/s10549-005-9016-8.CrossRefPubMed Martin MD, Hilsenbeck SG, Mohsin SK, Hopp TA, Clark GM, Osborne CK, Allred DC, O’Connell P: Breast tumors that overexpress nuclear metastasis-associated 1 (MTA1) protein have high recurrence risks but enhanced responses to systemic therapies. Breast Cancer Res Treat. 2006, 95: 7-12. 10.1007/s10549-005-9016-8.CrossRefPubMed
15.
go back to reference Ryu SH, Chung YH, Lee H, Kim JA, Shin HD, Min HJ, Seo DD, Jang MK, Yu E, Kim KW: Metastatic tumor antigen 1 is closely associated with frequent postoperative recurrence and poor survival in patients with hepatocellular carcinoma. Hepatology. 2008, 47: 929-936. 10.1002/hep.22124.CrossRefPubMed Ryu SH, Chung YH, Lee H, Kim JA, Shin HD, Min HJ, Seo DD, Jang MK, Yu E, Kim KW: Metastatic tumor antigen 1 is closely associated with frequent postoperative recurrence and poor survival in patients with hepatocellular carcinoma. Hepatology. 2008, 47: 929-936. 10.1002/hep.22124.CrossRefPubMed
16.
go back to reference Kawasaki G, Yanamoto S, Yoshitomi I, Yamada S, Mizuno A: Overexpression of metastasis-associated MTA1 in oral squamous cell carcinomas: correlation with metastasis and invasion. Int J Oral Maxillofac Surg. 2008, 37: 1039-1046. 10.1016/j.ijom.2008.05.020.CrossRefPubMed Kawasaki G, Yanamoto S, Yoshitomi I, Yamada S, Mizuno A: Overexpression of metastasis-associated MTA1 in oral squamous cell carcinomas: correlation with metastasis and invasion. Int J Oral Maxillofac Surg. 2008, 37: 1039-1046. 10.1016/j.ijom.2008.05.020.CrossRefPubMed
17.
go back to reference Zhu X, Guo Y, Li X, Ding Y, Chen L: Metastasis-associated protein 1 nuclear expression is associated with tumor progression and clinical outcome in patients with non-small cell lung cancer. J Thorac Oncol. 2010, 5: 1159-1166. 10.1097/JTO.0b013e3181e04d98.CrossRefPubMed Zhu X, Guo Y, Li X, Ding Y, Chen L: Metastasis-associated protein 1 nuclear expression is associated with tumor progression and clinical outcome in patients with non-small cell lung cancer. J Thorac Oncol. 2010, 5: 1159-1166. 10.1097/JTO.0b013e3181e04d98.CrossRefPubMed
18.
go back to reference Li SH, Tian H, Yue WM, Li L, Li WJ, Chen ZT, Hu WS, Zhu YC, Qi L: Overexpression of metastasis-associated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer. Ann Surg Oncol. 2011, 18: 2048-2056. 10.1245/s10434-010-1510-5.CrossRefPubMed Li SH, Tian H, Yue WM, Li L, Li WJ, Chen ZT, Hu WS, Zhu YC, Qi L: Overexpression of metastasis-associated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer. Ann Surg Oncol. 2011, 18: 2048-2056. 10.1245/s10434-010-1510-5.CrossRefPubMed
19.
go back to reference Du B, Yang ZY, Zhong XY, Fang M, Yan YR, Qi GL, Pan YL, Zhou XL: Metastasis-associated protein 1 induces VEGF-C and facilitates lymphangiogenesis in colorectal cancer. World J Gastroenterol. 2011, 17: 1219-1226. 10.3748/wjg.v17.i9.1219.CrossRefPubMedPubMedCentral Du B, Yang ZY, Zhong XY, Fang M, Yan YR, Qi GL, Pan YL, Zhou XL: Metastasis-associated protein 1 induces VEGF-C and facilitates lymphangiogenesis in colorectal cancer. World J Gastroenterol. 2011, 17: 1219-1226. 10.3748/wjg.v17.i9.1219.CrossRefPubMedPubMedCentral
20.
go back to reference Li SH, Tian H, Yue WM, Li L, Gao C, Li WJ, Hu WS, Hao B: Metastasis-associated protein 1 nuclear expression is closely associated with tumor progression and angiogenesis in patients with esophageal squamous cell cancer. World J Surg. 2012, 36: 623-631. 10.1007/s00268-011-1421-z.CrossRefPubMed Li SH, Tian H, Yue WM, Li L, Gao C, Li WJ, Hu WS, Hao B: Metastasis-associated protein 1 nuclear expression is closely associated with tumor progression and angiogenesis in patients with esophageal squamous cell cancer. World J Surg. 2012, 36: 623-631. 10.1007/s00268-011-1421-z.CrossRefPubMed
21.
go back to reference Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A: AJCC Cancer Staging Manual. 2010, Springer, New York, 7 Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A: AJCC Cancer Staging Manual. 2010, Springer, New York, 7
22.
go back to reference Kaplan EL, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc. 1958, 53: 457-481. 10.1080/01621459.1958.10501452.CrossRef Kaplan EL, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc. 1958, 53: 457-481. 10.1080/01621459.1958.10501452.CrossRef
23.
go back to reference Cox DR: Regression models and life tables. J R Stat Soc B. 1972, 34: 187-220. Cox DR: Regression models and life tables. J R Stat Soc B. 1972, 34: 187-220.
24.
go back to reference Deng Y, Zhou D, Zeng L: Expression and significance of MTA1 and RECK gene in nasopharyngeal carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011, 25: 534-538.PubMed Deng Y, Zhou D, Zeng L: Expression and significance of MTA1 and RECK gene in nasopharyngeal carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011, 25: 534-538.PubMed
25.
go back to reference Chen QY, Wen YF, Guo L, Liu H, Huang PY, Mo HY, Li NW, Xiang YQ, Luo DH, Qiu F: Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011, 103: 1761-1770. 10.1093/jnci/djr432.CrossRefPubMed Chen QY, Wen YF, Guo L, Liu H, Huang PY, Mo HY, Li NW, Xiang YQ, Luo DH, Qiu F: Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011, 103: 1761-1770. 10.1093/jnci/djr432.CrossRefPubMed
26.
go back to reference Yoo YG, Kong G, Lee MO: Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. EMBO J. 2006, 25: 1231-1241. 10.1038/sj.emboj.7601025.CrossRefPubMedPubMedCentral Yoo YG, Kong G, Lee MO: Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. EMBO J. 2006, 25: 1231-1241. 10.1038/sj.emboj.7601025.CrossRefPubMedPubMedCentral
27.
go back to reference Kai L, Wang J, Ivanovic M, Chung YT, Laskin WB, Schulze-Hoepfner F, Mirochnik Y, Satcher RL, Levenson AS: Targeting prostate cancer angiogenesis through metastasis-associated protein 1 (MTA1). Prostate. 2011, 71: 268-280. 10.1002/pros.21240.CrossRefPubMed Kai L, Wang J, Ivanovic M, Chung YT, Laskin WB, Schulze-Hoepfner F, Mirochnik Y, Satcher RL, Levenson AS: Targeting prostate cancer angiogenesis through metastasis-associated protein 1 (MTA1). Prostate. 2011, 71: 268-280. 10.1002/pros.21240.CrossRefPubMed
28.
go back to reference Yan C, Wang H, Toh Y, Boyd DD: Repression of 92-kDa type IV collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism, which is both dependent on and independent of histone deacetylation. J Biol Chem. 2003, 278: 2309-2316. 10.1074/jbc.M210369200.CrossRefPubMed Yan C, Wang H, Toh Y, Boyd DD: Repression of 92-kDa type IV collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism, which is both dependent on and independent of histone deacetylation. J Biol Chem. 2003, 278: 2309-2316. 10.1074/jbc.M210369200.CrossRefPubMed
29.
go back to reference Zhang H, Stephens LC, Kumar R: Metastasis tumor antigen family proteins during breast cancer progression and metastasis in a reliable mouse model for human breast cancer. Clin Cancer Res. 2006, 12: 1479-1486. 10.1158/1078-0432.CCR-05-1519.CrossRefPubMed Zhang H, Stephens LC, Kumar R: Metastasis tumor antigen family proteins during breast cancer progression and metastasis in a reliable mouse model for human breast cancer. Clin Cancer Res. 2006, 12: 1479-1486. 10.1158/1078-0432.CCR-05-1519.CrossRefPubMed
30.
go back to reference Hofer MD, Menke A, Genze F, Gierschik P, Giehl K: Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells. Br J Cancer. 2004, 90: 455-462. 10.1038/sj.bjc.6601535.CrossRefPubMedPubMedCentral Hofer MD, Menke A, Genze F, Gierschik P, Giehl K: Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells. Br J Cancer. 2004, 90: 455-462. 10.1038/sj.bjc.6601535.CrossRefPubMedPubMedCentral
31.
go back to reference Zhang XY, DeSalle LM, Patel JH, Capobianco AJ, Yu D, Thomas-Tikhonenko A, McMahon SB: Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein. Proc Natl Acad Sci U S A. 2005, 102: 13968-13973. 10.1073/pnas.0502330102.CrossRefPubMedPubMedCentral Zhang XY, DeSalle LM, Patel JH, Capobianco AJ, Yu D, Thomas-Tikhonenko A, McMahon SB: Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein. Proc Natl Acad Sci U S A. 2005, 102: 13968-13973. 10.1073/pnas.0502330102.CrossRefPubMedPubMedCentral
32.
go back to reference Lee SH, Chung YH, Kim JA, Lee D, Jin YJ, Shim JH, Jang MK, Cho EY, Shin ES, Lee JE: Single nucleotide polymorphisms associated with metastatic tumour antigen 1 overexpression in patients with hepatocellular carcinoma. Liver Int. 2012, 32: 457-466.PubMed Lee SH, Chung YH, Kim JA, Lee D, Jin YJ, Shim JH, Jang MK, Cho EY, Shin ES, Lee JE: Single nucleotide polymorphisms associated with metastatic tumour antigen 1 overexpression in patients with hepatocellular carcinoma. Liver Int. 2012, 32: 457-466.PubMed
Metadata
Title
Nuclear overexpression of metastasis-associated protein 1 correlates significantly with poor survival in nasopharyngeal carcinoma
Authors
Wen-Fei Li
Na Liu
Rui-Xue Cui
Qing-Mei He
Mo Chen
Ning Jiang
Ying Sun
Jing Zeng
Li-Zhi Liu
Jun Ma
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-78

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