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Promoter hypermethylation of SHOX2 and SEPT9 is a potential biomarker for minimally invasive diagnosis in adenocarcinomas of the biliary tract

Overview of attention for article published in Clinical Epigenetics, December 2016
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  • High Attention Score compared to outputs of the same age and source (86th percentile)

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Title
Promoter hypermethylation of SHOX2 and SEPT9 is a potential biomarker for minimally invasive diagnosis in adenocarcinomas of the biliary tract
Published in
Clinical Epigenetics, December 2016
DOI 10.1186/s13148-016-0299-x
Pubmed ID
Authors

V. Branchi, P. Schaefer, A. Semaan, A. Kania, P. Lingohr, J. C. Kalff, N. Schäfer, G. Kristiansen, D. Dietrich, H. Matthaei

Abstract

Biliary tract carcinoma (BTC) is a fatal malignancy which aggressiveness contrasts sharply with its relatively mild and late clinical presentation. Novel molecular markers for early diagnosis and precise treatment are urgently needed. The purpose of this study was to evaluate the diagnostic and prognostic value of promoter hypermethylation of the SHOX2 and SEPT9 gene loci in BTC. Relative DNA methylation of SHOX2 and SEPT9 was quantified in tumor specimens and matched normal adjacent tissue (NAT) from 71 BTC patients, as well as in plasma samples from an independent prospective cohort of 20 cholangiocarcinoma patients and 100 control patients. Receiver operating characteristic (ROC) curve analyses were performed to probe the diagnostic ability of both methylation markers. DNA methylation was correlated to clinicopathological data and to overall survival. SHOX2 methylation was significantly higher in tumor tissue than in NAT irrespective of tumor localization (p < 0.001) and correctly identified 71% of BTC specimens with 100% specificity (AUC = 0.918; 95% CI 0.865-0.971). SEPT9 hypermethylation was significantly more frequent in gallbladder carcinomas compared to cholangiocarcinomas (p = 0.01) and was associated with large primary tumors (p = 0.01) as well as age (p = 0.03). Cox proportional hazard analysis confirmed microscopic residual tumor at the surgical margin (R1-resection) as an independent prognostic factor, while SHOX2 and SEPT9 methylation showed no correlation with overall survival. Elevated DNA methylation levels were also found in plasma derived from cholangiocarcinoma patients. SHOX2 and SEPT9 methylation as a marker panel achieved a sensitivity of 45% and a specificity of 99% in differentiating between samples from patients with and without cholangiocarcinoma (AUC = 0.752; 95% CI 0.631-0.873). SHOX2 and SEPT9 are frequently methylated in biliary tract cancers. Promoter hypermethylation of SHOX2 and SEPT9 may therefore serve as a minimally invasive biomarker supporting diagnosis finding and therapy monitoring in clinical specimens.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 14%
Student > Ph. D. Student 5 12%
Professor > Associate Professor 4 10%
Student > Bachelor 3 7%
Student > Doctoral Student 2 5%
Other 6 14%
Unknown 16 38%
Readers by discipline Count As %
Medicine and Dentistry 11 26%
Biochemistry, Genetics and Molecular Biology 10 24%
Unspecified 2 5%
Agricultural and Biological Sciences 2 5%
Nursing and Health Professions 1 2%
Other 0 0%
Unknown 16 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 06 February 2023.
All research outputs
#6,867,131
of 24,413,320 outputs
Outputs from Clinical Epigenetics
#467
of 1,378 outputs
Outputs of similar age
#120,118
of 427,809 outputs
Outputs of similar age from Clinical Epigenetics
#4
of 22 outputs
Altmetric has tracked 24,413,320 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 1,378 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one has gotten more attention than average, scoring higher than 65% of its peers.
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 427,809 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.