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High levels of 5-hydroxymethylcytosine (5hmC) is an adverse predictor of biochemical recurrence after prostatectomy in ERG-negative prostate cancer

Overview of attention for article published in Clinical Epigenetics, October 2015
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Title
High levels of 5-hydroxymethylcytosine (5hmC) is an adverse predictor of biochemical recurrence after prostatectomy in ERG-negative prostate cancer
Published in
Clinical Epigenetics, October 2015
DOI 10.1186/s13148-015-0146-5
Pubmed ID
Authors

Siri H. Strand, Soren Hoyer, Anne-Sofie Lynnerup, Christa Haldrup, Tine Maj Storebjerg, Michael Borre, Torben F. Orntoft, Karina D. Sorensen

Abstract

Prostate cancer (PC) can be stratified into distinct molecular subtypes based on TMPRSS2-ERG gene fusion status, but its potential prognostic value remains controversial. Likewise, routine clinicopathological features cannot clearly distinguish aggressive from indolent tumors at the time of diagnosis; thus, new prognostic biomarkers are urgently needed. The DNA methylation variant 5-hydroxymethylcytosine (5hmC, an oxidized derivative of 5-methylcytosine) has recently emerged as a new diagnostic and/or prognostic biomarker candidate for several human malignancies. However, this remains to be systematically investigated for PC. In this study, we determined 5hmC levels in 311 PC (stratified by ERG status) and 228 adjacent non-malignant (NM) prostate tissue specimens by immunohistochemical analysis of a tissue microarray, representing a large radical prostatectomy (RP) cohort with long clinical follow-up. We investigated possible correlations between 5hmC and routine clinicopathological variables and assessed the prognostic potential of 5hmC by Kaplan-Meier and uni- and multivariate Cox regression analyses in ERG+ (n = 178) vs. ERG- (n = 133) PCs using biochemical recurrence (BCR) as endpoint. We observed a borderline significant (p = 0.06) reduction in 5hmC levels in PC compared to NM tissue samples, which was explained by a highly significant (p < 0.001) loss of 5hmC in ERG- PCs. ERG status was not predictive of BCR in this cohort (p = 0.73), and no significant association was found between BCR and 5hmC levels in ERG+ PCs (p = 0.98). In contrast, high 5hmC immunoreactivity was a significant adverse predictor of BCR after RP in ERG- PCs, independent of Gleason score, pathological tumor stage, surgical margin status, and pre-operative prostate-specific antigen (PSA) level (hazard ratio (HR) (95 % confidence interval (CI)): 1.62 (1.15-2.28), p = 0.006). This is the first study to demonstrate a prognostic potential for 5hmC in PC. Our findings highlight the importance of ERG stratification in PC biomarker studies and suggest that epigenetic mechanisms involving 5hmC are important for the development and/or progression of ERG- PC.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 4%
Unknown 25 96%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 15%
Researcher 4 15%
Student > Postgraduate 3 12%
Student > Ph. D. Student 2 8%
Student > Doctoral Student 1 4%
Other 3 12%
Unknown 9 35%
Readers by discipline Count As %
Medicine and Dentistry 6 23%
Biochemistry, Genetics and Molecular Biology 4 15%
Agricultural and Biological Sciences 3 12%
Mathematics 1 4%
Chemistry 1 4%
Other 0 0%
Unknown 11 42%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 12 November 2015.
All research outputs
#13,973,415
of 24,716,872 outputs
Outputs from Clinical Epigenetics
#680
of 1,406 outputs
Outputs of similar age
#127,265
of 284,632 outputs
Outputs of similar age from Clinical Epigenetics
#28
of 32 outputs
Altmetric has tracked 24,716,872 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,406 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.2. This one has gotten more attention than average, scoring higher than 50% 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 284,632 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 54% of its contemporaries.
We're also able to compare this research output to 32 others from the same source and published within six weeks on either side of this one. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.