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Epigenetic regulation and role of metastasis suppressor genes in pancreatic ductal adenocarcinoma

Overview of attention for article published in BMC Cancer, May 2013
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Title
Epigenetic regulation and role of metastasis suppressor genes in pancreatic ductal adenocarcinoma
Published in
BMC Cancer, May 2013
DOI 10.1186/1471-2407-13-264
Pubmed ID
Authors

Wolf Arif Mardin, Joerg Haier, Soeren Torge Mees

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is distinguished by rapid dissemination. Thus, genetic and/or epigenetic deregulation of metastasis suppressor genes (MSG) is a likely event during early pancreatic carcinogenesis and a potential diagnostic marker for the disease. We investigated 9 known MSGs for their role in the dissemination of PDAC and examined their promoters for methylation and its use in PDAC detection. MRNA expression of 9 MSGs was determined in 18 PDAC cell lines by quantitative RT-PCR and promoter methylation was analyzed by Methylation Specific PCR and validated by Bisulfite Sequencing PCR. These data were compared to the cell lines' in vivo metastatic and invasive potential that had been previously established. Statistical analysis was performed with SPSS 20 using 2-tailed Spearman's correlation with P < 0.05 being considered significant. Complete downregulation of MSG-mRNA expression in PDAC cell lines vs. normal pancreatic RNA occurred in only 1 of 9 investigated genes. 3 MSGs (CDH1, TIMP3 and KiSS-1) were significantly methylated. Methylation only correlated to loss of mRNA expression in CDH1 (P < 0.05). Bisulfite Sequencing PCR showed distinct methylation patterns, termed constant and variable methylation, which could distinguish methylation-regulated from non methylation-regulated genes. Higher MSG mRNA-expression did not correlate to less aggressive PDAC-phenotypes (P > 0.14). Genes with metastasis suppressing functions in other tumor entities did not show evidence of assuming the same role in PDAC. Inactivation of MSGs by promoter methylation was an infrequent event and unsuitable as a diagnostic marker of PDAC. A distinct methylation pattern was identified, that resulted in reduced mRNA expression in all cases. Thus, constant methylation patterns could predict regulatory significance of a promoter's methylation prior to expression analysis and hence present an additional tool during target gene selection.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 4%
France 1 4%
Unknown 23 92%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 7 28%
Student > Ph. D. Student 4 16%
Researcher 4 16%
Student > Doctoral Student 2 8%
Lecturer 1 4%
Other 6 24%
Unknown 1 4%
Readers by discipline Count As %
Medicine and Dentistry 9 36%
Biochemistry, Genetics and Molecular Biology 6 24%
Agricultural and Biological Sciences 5 20%
Computer Science 1 4%
Nursing and Health Professions 1 4%
Other 0 0%
Unknown 3 12%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 May 2013.
All research outputs
#20,194,150
of 22,711,242 outputs
Outputs from BMC Cancer
#6,484
of 8,263 outputs
Outputs of similar age
#170,186
of 195,178 outputs
Outputs of similar age from BMC Cancer
#90
of 97 outputs
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So far Altmetric has tracked 8,263 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 97 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.