Source:http://linkedlifedata.com/resource/pubmed/id/19020732
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2008-11-21
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1021-335X
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pubmed:author |
pubmed-author:FujimuraTakashiT,
pubmed-author:FunakiHiroshiH,
pubmed-author:FushidaSachioS,
pubmed-author:KawakamiKazuyukiK,
pubmed-author:KayaharaMasatoM,
pubmed-author:KitagawaHirohisaH,
pubmed-author:NakagawaraHisatoshiH,
pubmed-author:NinomiyaItasuI,
pubmed-author:OhtaTetsuoT,
pubmed-author:TajimaHidehiroH,
pubmed-author:TakamuraHiroyukiH
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pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1489-95
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pubmed:meshHeading |
pubmed-meshheading:19020732-Carcinoma, Squamous Cell,
pubmed-meshheading:19020732-DNA Methylation,
pubmed-meshheading:19020732-Disease-Free Survival,
pubmed-meshheading:19020732-Esophageal Neoplasms,
pubmed-meshheading:19020732-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19020732-Humans,
pubmed-meshheading:19020732-Mucous Membrane,
pubmed-meshheading:19020732-Neoplasm Invasiveness,
pubmed-meshheading:19020732-Neoplasm Metastasis,
pubmed-meshheading:19020732-Polymerase Chain Reaction,
pubmed-meshheading:19020732-Prognosis,
pubmed-meshheading:19020732-Proportional Hazards Models,
pubmed-meshheading:19020732-Sulfites,
pubmed-meshheading:19020732-Tissue Inhibitor of Metalloproteinase-3,
pubmed-meshheading:19020732-Treatment Outcome
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pubmed:year |
2008
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pubmed:articleTitle |
Quantitative detection of TIMP-3 promoter hypermethylation and its prognostic significance in esophageal squamous cell carcinoma.
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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
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pubmed:publicationType |
Journal Article
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