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Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer

Overview of attention for article published in BMC Cancer, February 2016
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Title
Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer
Published in
BMC Cancer, February 2016
DOI 10.1186/s12885-016-2135-2
Pubmed ID
Authors

Gabriel Schmid, Sara Notaro, Daniel Reimer, Samira Abdel-Azim, Michaela Duggan-Peer, Jessica Holly, Heidi Fiegl, Julia Rössler, Annemarie Wiedemair, Nicole Concin, Peter Altevogt, Christian Marth, Alain Gustave Zeimet

Abstract

An increasing body of evidence shows that miR-34 family has tumor suppressive properties mediating apoptosis, cell cycle arrest and senescence. In ovarian cancer, miR34 family members were found to be under expressed. Particularly miR-34a has been revealed to be a direct transcriptional target of p53 which is frequently mutated in epithelial ovarian carcinomas especially in high grade serous cancer. Moreover, methylation of miR-34a CpG Islands was found to down-regulate miR-34a expression. The aim of this study was to investigate the clinical relevance of mir34a as well as its promoter methylation in a subset of 133 ovarian cancers with a special focus on the p53 mutation status, the dualistic type I and type II ovarian cancer model and the different histotypes. One hundred thirty-three epithelial ovarian cancers and 8 samples of healthy ovarian surface epithelium were retrospectively analysed for miR-34a expression with quantitative real-time reverse transcription PCR (qRT-PCR). Gene-specific DNA methylation was evaluated with MethyLight technique. Significantly lower miR-34a expression was found in ovarian cancers than in healthy ovarian epithelium (p = 0.002). The expression of miR-34a was found lower in type II than in type I cancers (p = 0.037), in p53 mutated as compared to p53 wild type cancers (p = 0.003) and in high grade compared to in low grade cancers (p = 0.028). In multivariate COX regression model low expressing miR-34a cancers exhibited a reduced PFS (p = 0.039) and OS (p = 0.018). In serous cancers low miR-34a levels showed a worse OS confirmed also in multivariate analysis (p = 0.022). miR-34a promoter methylation was found higher in type II cancers than in type I (p = 0.006). mir34a expression and promoter methylation showed an inverse correlation in cancer samples (p = 0.05). We demonstrated a clinical independent role of miR-34a in epithelial ovarian cancers. Moreover, we corroborated the correlation between miR-34a expression and its promoter methylation in a large set of ovarian cancers. The inverse association between miR-34a expression and grading, p53 mutation status and dualistic tumor type classification, together with its prognostic relevance may underline the tumor-suppressive character of miR-34a in ovarian cancer.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 52 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 27%
Researcher 6 12%
Student > Master 6 12%
Student > Bachelor 3 6%
Professor > Associate Professor 3 6%
Other 3 6%
Unknown 17 33%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 29%
Agricultural and Biological Sciences 7 13%
Medicine and Dentistry 6 12%
Immunology and Microbiology 2 4%
Nursing and Health Professions 1 2%
Other 1 2%
Unknown 20 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 18 February 2016.
All research outputs
#14,249,851
of 22,849,304 outputs
Outputs from BMC Cancer
#3,365
of 8,314 outputs
Outputs of similar age
#212,428
of 403,162 outputs
Outputs of similar age from BMC Cancer
#67
of 185 outputs
Altmetric has tracked 22,849,304 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,314 research outputs from this source. They receive a mean Attention Score of 4.3. This one has gotten more attention than average, scoring higher than 56% 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 403,162 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 185 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.