title: MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma.
abstract: The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.
authors.affiliation: Department of Oncology, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
authors.forename: Hong-Hua
authors.initials: HH
authors.lastname: Peng
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Pei-Guo
authors.initials: PG
authors.lastname: Cao
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D044463:Receptor, PAR-1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009363:Neoplasm Proteins; D044463:Receptor, PAR-1; D020781:Matrix Metalloproteinase 1
references.citation: Ann Surg Oncol. 2009 Feb;16(2):506-14
references.pmid: 19050962
references.citation: Nat Rev Cancer. 2006 Jun;6(6):449-58
references.pmid: 16723991
references.citation: J Transl Med. 2010 Oct 14;8:99
references.pmid: 20946664
references.citation: Stem Cells. 2009 Jun;27(6):1366-75
references.pmid: 19489099
references.citation: Tumour Biol. 2006;27(3):133-41
references.pmid: 16641547
references.citation: Cancer. 1992 Dec 15;70(12):2747-53
references.pmid: 1451050
references.citation: Clin Exp Metastasis. 2007;24(7):541-50
references.pmid: 17668281
references.citation: Oncogene. 2003 May 19;22(20):3130-7
references.pmid: 12789289
references.citation: Am J Gastroenterol. 2005 Aug;100(8):1835-43
references.pmid: 16086722
references.citation: Pol Arch Med Wewn. 2009 Sep;119(9):558-63
references.pmid: 19776700
references.citation: Cancer Res. 2004 Oct 1;64(19):6965-72
references.pmid: 15466188
references.citation: Cancer Cell. 2005 Mar;7(3):207-8
references.pmid: 15766657
references.citation: DNA Cell Biol. 2008 Oct;27(10):553-7
references.pmid: 18680431
references.citation: Oncogene. 2009 Dec 3;28(48):4237-48
references.pmid: 19734937
references.citation: Integr Cancer Ther. 2011 Mar;10(1):58-69
references.pmid: 20702488
references.citation: J Korean Med Sci. 2011 Apr;26(4):513-20
references.pmid: 21468258
references.citation: Annu Rev Cell Dev Biol. 2001;17:463-516
references.pmid: 11687497
references.citation: Gynecol Oncol. 2011 Feb;120(2):247-55
references.pmid: 21093894
references.citation: FASEB J. 2003 Feb;17(2):163-74
references.pmid: 12554695
references.citation: Microvasc Res. 2011 Jan;81(1):108-16
references.pmid: 20923679
references.citation: Cancer Res. 2010 Jul 15;70(14):5880-90
references.pmid: 20570895
references.citation: PLoS One. 2011 Mar 31;6(3):e18219
references.pmid: 21483813
references.citation: Biomarkers. 2010 Dec;15(8):684-92
references.pmid: 20860530
references.citation: Cell. 2005 Feb 11;120(3):303-13
references.pmid: 15707890
references.citation: Clin Cancer Res. 2000 Mar;6(3):1169-74
references.pmid: 10741748
references.citation: World J Gastroenterol. 2011 Mar 14;17(10):1373-8
references.pmid: 21455340
references.citation: J Autoimmun. 2009 Nov-Dec;33(3-4):214-21
references.pmid: 19800199
references.citation: Folia Histochem Cytobiol. 2008;46(4):471-8
references.pmid: 19141401
references.citation: Biochim Biophys Acta. 2011 Mar;1809(3):200-10
references.pmid: 21241837
references.citation: Nat Med. 2005 May;11(5):481-3
references.pmid: 15864312
references.citation: Hepatogastroenterology. 2010 Nov-Dec;57(104):1423-9
references.pmid: 21443097