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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-7-12
pubmed:abstractText
Fibulin-3 gene has been identified as an antagonist of angiogenesis. We investigated the protein expression and promoter methylation status of fibulin-3 gene in colorectal cancer (CRC) and analyzed its correlation with clinicopathological factors. The study population enrolled 85 paired CRC specimens and adjacent normal tissues, as well as 32 cases of colorectal adenoma. Genomic DNA was extracted from paraffin-embedded samples using manual microdissection. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status and fibulin-3 gene expression was detected by immunohistochemistry. The results showed that, downregulation or silence of fibulin-3 protein was found in 57.6% (49/85) of CRC tissues, which was significantly higher than that of adjacent normal tissues (28.2%, 24/85) and colorectal adenoma (34.4%, 11/32) (P<0.05). Furthermore, 33 out of 85 (38.8%) CRC specimens showed hypermethylation in fibulin-3 promoter region, and fibulin-3 methylation was closely correlated with its loss of expression. Also, downregulation of fibulin-3 was associated with advanced stage (P=0.008) and lymph node metastasis (P=0.013). Survival analyses and Cox proportional hazard models indicated that fibulin-3 downregulation was an independent factor related to adverse overall survival (OS) and disease-free survival (DFS) of CRC. In conclusion, we found aberrant methylation caused fibulin-3 downregulation in CRC, and fibulin-3 downregulation was correlated with tumor stage, lymph node metastasis and poor survival, which maybe use as a potential prognostic factor for CRC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0028-2685
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
441-8
pubmed:meshHeading
pubmed-meshheading:21744999-Adenoma, pubmed-meshheading:21744999-Adult, pubmed-meshheading:21744999-Aged, pubmed-meshheading:21744999-Aged, 80 and over, pubmed-meshheading:21744999-Colorectal Neoplasms, pubmed-meshheading:21744999-DNA Methylation, pubmed-meshheading:21744999-Down-Regulation, pubmed-meshheading:21744999-Extracellular Matrix Proteins, pubmed-meshheading:21744999-Female, pubmed-meshheading:21744999-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21744999-Humans, pubmed-meshheading:21744999-Immunoenzyme Techniques, pubmed-meshheading:21744999-Lymphatic Metastasis, pubmed-meshheading:21744999-Male, pubmed-meshheading:21744999-Middle Aged, pubmed-meshheading:21744999-Neoplasm Staging, pubmed-meshheading:21744999-Polymerase Chain Reaction, pubmed-meshheading:21744999-Prognosis, pubmed-meshheading:21744999-Promoter Regions, Genetic, pubmed-meshheading:21744999-Survival Rate
pubmed:year
2011
pubmed:articleTitle
Downregulation of fibulin-3 gene by promoter methylation in colorectal cancer predicts adverse prognosis.
pubmed:affiliation
Department of Oncology, Yangzhou No.1 People Hospital, The Second Clinical School of Yangzhou University, Yangzhou, China. tongjd1@yahoo.cn
pubmed:publicationType
Journal Article