Top

Published in:

01-04-2013

Close Association of Metastasis-Associated Protein 1 Overexpression with Increased Angiogenesis and Poor Survival in Patients with Histologically Node-Negative Gastric Cancer

Authors: Xiaomei Deng, Lutao Du, Chuanxin Wang, Yongmei Yang, Juan Li, Hui Liu, Jian Zhang, Lili Wang, Xin Zhang, Wei Li, Xuhua Zhang, Shun Wang, Zhaogang Dong

Published in: World Journal of Surgery | Issue 4/2013

Abstract

Background

Although metastasis-associated protein 1 (MTA1) has been recently demonstrated as a potent angiogenesis-promoting factor in various malignant tumors, its angiogenic property in gastric cancer (GC) remains unclear. This study has detected the expression of MTA1 protein in surgically resected tissues of pathologic N0 (pN0) GC and further investigated its relation with other clinicopathologic factors and tumor angiogenesis and prognosis.

Methods

MTA1 protein expression was detected immunohistochemically in 111 pN0 GC specimens. Its correlations with clinicopathologic factors and tumor prognosis were evaluated. The intratumoral microvessel density (MVD) was assessed based on CD105 antigen immunoreactivity and analyzed for correlation with MTA1 protein expression.

Results

Overexpression of MTA1 was detected in 36.04 % of patients and exhibited a significant association with tumor size and MVD. Survival analysis demonstrated that both overall (OS) and disease-free (DFS) survivals in patients overexpressing MTA1 were significantly poorer than those without MTA1 overexpression 5 years after the operation (both p < 0.001). Multivariate survival analysis demonstrated that MTA1 overexpression was an independent prognosticator for unfavorable OS and DFS (p < 0.001, respectively).

Conclusions

MTA1 overexpression is frequently observed in pN0 GC patients and is significantly associated with increased angiogenesis and poor prognosis. Detection of MTA1 protein expression may help predict the relapse and prognosis of pN0 GC. Also, MTA1 protein may form a novel target for antiangiogenic therapy.

Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRef

Zheng L, Wang L, Ajani J et al (2004) Molecular basis of gastric cancer development and progression. Gastric Cancer 7:61–77PubMedCrossRef

Brennan MF (2005) Current status of surgery for gastric cancer: a review. Gastric Cancer 8:64–70PubMedCrossRef

Alberts SR, Cervantes A, van de Velde CJ (2003) Gastric cancer: epidemiology, pathology and treatment. Ann Oncol 14(Suppl 2):31–36

Ichikura T, Tomimatsu S, Uefuji K et al (1999) Evaluation of the New American Joint Committee on Cancer/International Union Against Cancer classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification. Cancer 86:553–558PubMedCrossRef

Nicolson GL, Nawa A, Toh Y et al (2003) Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clin Exp Metastasis 20:19–24PubMedCrossRef

Kumar R, Wang RA, Bagheri-Yarmand R (2003) Emerging roles of MTA family members in human cancers. Semin Oncol 30:30–37PubMedCrossRef

Mazumdar A, Wang RA, Mishra SK et al (2001) Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol 3:30–37PubMedCrossRef

Yan C, Wang H, Toh Y et al (2003) 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 278:2309–2316PubMedCrossRef

10.

Toh Y, Pencil SD, Nicolson GL (1994) 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 269:22958–22963PubMed

11.

Toh Y, Pencil SD, Nicolson GL (1995) Analysis of the complete sequence of the novel metastasis-associated candidate gene, mta1, differentially expressed in mammary adenocarcinoma and breast cancer cell lines. Gene 159:97–104PubMedCrossRef

12.

Li SH, Wang Z, Liu XY (2009) Metastasis-associated protein 1 (MTA1) overexpression is closely associated with shorter disease-free interval after complete resection of histologically node-negative esophageal cancer. World J Surg 33:1876–1881PubMedCrossRef

13.

Jang KS, Paik SS, Chung H et al (2006) MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers. Cancer Sci 97:374–379PubMedCrossRef

14.

Li SH, Tian H, Yue WM et al (2011) 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 18:2048–2056PubMedCrossRef

15.

Kai L, Wang J, Ivanovic M et al (2011) Targeting prostate cancer angiogenesis through metastasis-associated protein 1 (MTA1). Prostate 71:268–280PubMedCrossRef

16.

Toh Y, Oki E, Oda S et al (1997) Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis. Int J Cancer 74:459–463PubMedCrossRef

17.

Arbiser JL (2005) Implications of Epstein-Barr Virus (EBV)-induced carcinogenesis on cutaneous inflammation and carcinogenesis: evidence of recurring patterns of angiogenesis and signal transduction. J Invest Dermatol 124:Xi–xiiPubMedCrossRef

18.

Onizuka S, Kawakami S, Taniguchi K et al (2004) Pancreatic carcinogenesis: apoptosis and angiogenesis. Pancreas 28:317–319PubMedCrossRef

19.

World Health Organization (1988) International Histological Classification of Tumours, 2nd edn. Geneva, World Health Organization, 1969–1981. Berlin, Springer

20.

Sobin LH, Wittekind CH (eds) (1997) TNM classification of malignant tumours, 5th edn. Wiley, New York

21.

Yu D, Zhuang L, Sun X et al (2007) Particular distribution and expression pattern of endoglin (CD105) in the liver of patients with hepatocellular carcinoma. BMC Cancer 7:122–131PubMedCrossRef

22.

Weidner N (1995) Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 36:169–180PubMedCrossRef

23.

Ryu SH, Chung YH, Lee H et al (2008) Metastatic tumor antigen 1 is closely associated with frequent postoperative recurrence and poor survival in patients with hepatocellular carcinoma. Hepatology 47:929–936PubMedCrossRef

Title: Close Association of Metastasis-Associated Protein 1 Overexpression with Increased Angiogenesis and Poor Survival in Patients with Histologically Node-Negative Gastric Cancer
Authors: Xiaomei Deng
Lutao Du
Chuanxin Wang
Yongmei Yang
Juan Li
Hui Liu
Jian Zhang
Lili Wang
Xin Zhang
Wei Li
Xuhua Zhang
Shun Wang
Zhaogang Dong
Publication date: 01-04-2013
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 4/2013
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-012-1898-0

At a glance: The STEP trials

Springer Medicine

Close Association of Metastasis-Associated Protein 1 Overexpression with Increased Angiogenesis and Poor Survival in Patients with Histologically Node-Negative Gastric Cancer

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2013

Colorectal Cancer and Crohn’s Colitis: Clinical Implications From 313 Surgical Patients

Laparoscopic Surgery for Rectal Cancer: Outcomes in 513 Patients

Effect of Adjusted Cuff Pressure of Endotracheal Tube During Thyroidectomy on Postoperative Airway Complications: Prospective, Randomized, and Controlled Trial

Blunt Hollow Viscus and Mesenteric Injury: Still Underrecognized

Single Port Laparoscopic Totally Extraperitoneal Hernioplasty: A Comparative Study of Short-term Outcome with Conventional Laparoscopic Totally Extraperitoneal Hernioplasty

Complex Hepatectomy under Total Vascular Exclusion of the Liver: Impact of Ischemic Preconditioning on Clinical Outcomes