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http://purl.uniprot.org/citations/23243217http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23243217http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Here, we determined whether epigenetic inactivation of miR-34a and miR-34b/c genes may serve as a prognostic marker for distant metastases in colon cancer.

Experimental design

Using a case-control study design of 94 primary colon cancer samples with and without liver metastases, we determined CpG methylation frequencies of miR-34a and miR-34b/c promoters, expression of miR-34a, and its targets c-Met, Snail, and β-catenin and their prognostic value.

Results

miR-34a methylation was detected in 45.1% (n = 42 of 93) of the samples and strongly associated with metastases to the liver (P = 0.003) and lymph nodes (P = 0.006). miR-34b/c methylation was detected in 91.9% of the samples (n = 79/86). A significant inverse correlation between miR-34a methylation and expression of mature miR-34a (P = 0.018) was detected. Decreased miR-34a expression was associated with upregulation of c-Met, Snail, and β-catenin protein levels (P = 0.031, 0.132, and 0.004), which were associated with distant metastases (P = 0.001, 0.017, and 0.005). In a confounder-adjusted multivariate regression model miR-34a methylation, high c-Met and β-catenin levels provided the most significant prognostic information about metastases to the liver (P = 0.014, 0.031, and 0.058) and matched pairs showed a higher prevalence of these risk factors in the samples with distant spread (P = 0.029). Finally, we obtained statistical evidence indicating that the simultaneous detection of these three markers has the highest prognostic value.

Conclusions

Silencing of miR-34a and upregulation of c-Met, Snail, and β-catenin expression is associated with liver metastases of colon cancer. Detection of miR-34a silencing in resected primary colon cancer may be of prognostic value, especially in combination with detection of c-Met and β-catenin expression."xsd:string
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http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/author"Hermeking H."xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/author"Horst D."xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/author"Kirchner T."xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/author"Neumann J."xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/author"Mansmann U."xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/author"Jackstadt R."xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/author"Siemens H."xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/name"Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/pages"710-720"xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/title"Detection of miR-34a promoter methylation in combination with elevated expression of c-Met and beta-catenin predicts distant metastasis of colon cancer."xsd:string
http://purl.uniprot.org/citations/23243217http://purl.uniprot.org/core/volume"19"xsd:string
http://purl.uniprot.org/citations/23243217http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23243217
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