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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-11-21
pubmed:abstractText
Tissue inhibitor of metalloproteinase-3 (TIMP-3) has an inhibitory effect on tumor development, growth and metastasis due to its interaction with matrix metalloproteinases (MMPs). We investigated the prognostic significance of TIMP-3 gene promoter methylation in esophageal squamous cell carcinoma (ESCC). TIMP-3 methylation was analyzed by MethyLight, a quantitative and methylation-specific PCR method. Hypermethylation was found in 9/51 (18%) surgically resected ESCC samples and was associated with reduced disease-free (p=0.0039) and overall survival (p=0.0047). Upon multivariate analysis, it was found to be an independent prognostic parameter for poor survival and was associated with earlier recurrence after surgery (p=0.0238), especially via pleural dissemination (p=0.001). Expression levels for TIMP-3 protein and for several MMPs were analyzed by Western blot analysis in 20 pairs of ESCC and adjacent normal tissue. The expression of MMP-2, -7 and -9 proteins in tumor tissue was significantly higher than in corresponding normal mucosa (p=0.0051, 0.0064 and 0.0004, respectively). In contrast, the expression of TIMP-3 protein in tumor tissue was significantly lower than in matched normal mucosa (p=0.0152). Tumors with TIMP-3 hypermethylation expressed lower levels of TIMP-3 protein compared to those without hypermethylation (p=0.0357). These results demonstrate that TIMP-3 hypermethylation is associated with lower TIMP-3 protein expression in ESCC and with poor patient survival due to a high frequency of recurrence by pleural dissemination.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1021-335X
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1489-95
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Quantitative detection of TIMP-3 promoter hypermethylation and its prognostic significance in esophageal squamous cell carcinoma.
pubmed:affiliation
Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-8641, Japan. nino@surg2.m.kanazawa-u.ac.jp
pubmed:publicationType
Journal Article