↓ Skip to main content

Silencing of Glutathione Peroxidase 3 through DNA Hypermethylation Is Associated with Lymph Node Metastasis in Gastric Carcinomas

Overview of attention for article published in PLOS ONE, October 2012
Altmetric Badge

Mentioned by

twitter
1 X user

Citations

dimensions_citation
60 Dimensions

Readers on

mendeley
34 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Silencing of Glutathione Peroxidase 3 through DNA Hypermethylation Is Associated with Lymph Node Metastasis in Gastric Carcinomas
Published in
PLOS ONE, October 2012
DOI 10.1371/journal.pone.0046214
Pubmed ID
Authors

Dun-Fa Peng, Tian-Ling Hu, Barbara G. Schneider, Zheng Chen, Ze-Kuan Xu, Wael El-Rifai

Abstract

Gastric cancer remains the second leading cause of cancer-related death in the world. H. pylori infection, a major risk factor for gastric cancer, generates high levels of reactive oxygen species (ROS). Glutathione peroxidase 3 (GPX3), a plasma GPX member and a major scavenger of ROS, catalyzes the reduction of hydrogen peroxide and lipid peroxides by reduced glutathione. To study the expression and gene regulation of GPX3, we examined GPX3 gene expression in 9 gastric cancer cell lines, 108 primary gastric cancer samples and 45 normal gastric mucosa adjacent to cancers using quantitative real-time RT-PCR. Downregulation or silencing of GPX3 was detected in 8 of 9 cancer cell lines, 83% (90/108) gastric cancers samples, as compared to non-tumor adjacent normal gastric samples (P<0.0001). Examination of GPX3 promoter demonstrated DNA hypermethylation (≥ 10% methylation level determined by Bisulfite Pyrosequencing) in 6 of 9 cancer cell lines and 60% of gastric cancer samples (P = 0.007). We also detected a significant loss of DNA copy number of GPX3 in gastric cancers (P<0.001). Treatment of SNU1 and MKN28 cells with 5-Aza-2' Deoxycytidine restored the GPX3 gene expression with a significant demethylation of GPX3 promoter. The downregulation of GPX3 expression and GPX3 promoter hypermethylation were significantly associated with gastric cancer lymph node metastasis (P = 0.018 and P = 0.029, respectively). We also observed downregulation, DNA copy number losses, and promoter hypermethylation of GPX3 in approximately one-third of tumor-adjacent normal gastric tissue samples, suggesting the presence of a field defect in areas near tumor samples. Reconstitution of GPX3 in AGS cells reduced the capacity of cell migration, as measured by scratch wound healing assay. Taken together, the dysfunction of GPX3 in gastric cancer is mediated by genetic and epigenetic alterations, suggesting impairment of mechanisms that regulate ROS and its possible involvement in gastric tumorigenesis and metastasis.

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 6%
Unknown 32 94%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 21%
Student > Ph. D. Student 5 15%
Student > Master 4 12%
Other 3 9%
Student > Doctoral Student 3 9%
Other 6 18%
Unknown 6 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 21%
Medicine and Dentistry 6 18%
Biochemistry, Genetics and Molecular Biology 5 15%
Engineering 3 9%
Nursing and Health Professions 1 3%
Other 4 12%
Unknown 8 24%
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 15 October 2012.
All research outputs
#15,253,344
of 22,681,577 outputs
Outputs from PLOS ONE
#129,867
of 193,576 outputs
Outputs of similar age
#108,141
of 172,656 outputs
Outputs of similar age from PLOS ONE
#2,850
of 4,570 outputs
Altmetric has tracked 22,681,577 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 193,576 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 172,656 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 4,570 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.