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TFF1 hypermethylation and decreased expression in esophageal squamous cell carcinoma and histologically normal tumor surrounding esophageal cells

Overview of attention for article published in Clinical Epigenetics, December 2017
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Title
TFF1 hypermethylation and decreased expression in esophageal squamous cell carcinoma and histologically normal tumor surrounding esophageal cells
Published in
Clinical Epigenetics, December 2017
DOI 10.1186/s13148-017-0429-0
Pubmed ID
Authors

Isabela Martins Gonzaga, Sheila Coelho Soares Lima, Marina Chianello Nicolau, Pedro Nicolau-Neto, Nathalia Meireles da Costa, Tatiana de Almeida Simão, Hector Hernandez-Vargas, Zdenko Herceg, Luis Felipe Ribeiro Pinto

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the 10 most incident cancer types in the world, and it is mainly associated with tobacco and alcohol consumption. ESCC mortality rates stand very close to its incidence, which is a direct consequence of a late diagnosis and an inefficient treatment. Although this scenery is quite alarming, the major molecular alterations that drive this carcinogenesis process remain unclear. We have previously shown through the first ESCC methylome analysis that TFF1 promoter is frequently hypermethylated in ESCC. Here, to evaluate TFF1 methylation as a potential biomarker of early ESCC diagnosis, we investigated the status of TFF1 promoter methylation and its expression in ESSC and histologically normal tumor surrounding tissue of ESCC patients in comparison to healthy esophagus of non-cancer individuals. Analysis of TFF1 promoter methylation, and gene and protein expression in 65 ESCC patients and 88 controls revealed that TFF1 methylation levels were already increased in histologically normal tumor surrounding tissue of ESCC patients when compared to healthy esophagus of non-cancer individuals. This increase in DNA methylation was followed by the reduction of TFF1 mRNA expression. Interestingly, TFF1 expression was capable of distinguishing tumor surrounding normal tissue from normal mucosa of healthy individuals with 92% accuracy. In addition, TFF1 protein was undetectable both in tumor and surrounding mucosa by immunohistochemistry, while submucosa glands of the healthy esophagus showed positive staining. Furthermore, treatment of TE-1 and TE-13 ESCC cell lines with decitabine led to a reduction of promoter methylation and consequent upregulation of TFF1 gene and protein expression. Finally, using TCGA data we showed that TFF1 loss is observed in ESCC, but not in esophageal adenocarcinoma, highlighting the different molecular mechanisms involved in the development of each histological subtype of esophageal cancer. This study shows that TFF1 expression is silenced in early phases of ESCC development, which seems to be mediated at least in part by promoter hypermethylation, and provides the basis for the use of TFF1 expression as a potential biomarker for early ESCC detection.

Twitter Demographics

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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 %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 10 29%
Student > Bachelor 6 18%
Student > Ph. D. Student 6 18%
Researcher 3 9%
Other 2 6%
Other 1 3%
Unknown 6 18%
Readers by discipline Count As %
Medicine and Dentistry 9 26%
Biochemistry, Genetics and Molecular Biology 6 18%
Agricultural and Biological Sciences 3 9%
Nursing and Health Professions 1 3%
Computer Science 1 3%
Other 3 9%
Unknown 11 32%

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 04 January 2018.
All research outputs
#10,971,879
of 12,381,422 outputs
Outputs from Clinical Epigenetics
#518
of 569 outputs
Outputs of similar age
#292,985
of 352,477 outputs
Outputs of similar age from Clinical Epigenetics
#29
of 39 outputs
Altmetric has tracked 12,381,422 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 569 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. 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 39 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.