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A novel DNA methylation panel accurately detects colorectal cancer independently of molecular pathway

Overview of attention for article published in Journal of Translational Medicine, February 2018
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Title
A novel DNA methylation panel accurately detects colorectal cancer independently of molecular pathway
Published in
Journal of Translational Medicine, February 2018
DOI 10.1186/s12967-018-1415-9
Pubmed ID
Authors

Micaela Freitas, Fábio Ferreira, Sónia Carvalho, Fernanda Silva, Paula Lopes, Luís Antunes, Sofia Salta, Francisca Diniz, Lúcio Lara Santos, José Flávio Videira, Rui Henrique, Carmen Jerónimo

Abstract

Colorectal cancer (CRC) is one of the most incident cancers, associated with significant morbidity and mortality, and usually classified into three main molecular pathways: chromosomal instability, microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Currently, available screening methods are either costly or of limited specificity, impairing global implementation. More cost-effective strategies, including DNA methylation-based tests, might prove advantageous. Although some are already available, its performance is suboptimal, entailing the need for better candidate biomarkers. Herein, we tested whether combined use of APC, IGF2, MGMT, RASSF1A, and SEPT9 promoter methylation might accurately detect CRC irrespective of molecular subtype. Selected genes were validated using formalin-fixed paraffin-embedded tissues from 214 CRC and 50 non-malignant colorectal mucosae (CRN). Promoter methylation levels were assessed using real-time quantitative methylation-specific PCR. MSI and CIMP status were determined. Molecular data were correlated with standard clinicopathological features. Diagnostic and prognostic performances were evaluated by receiver operator characteristics curve and survival analyses, respectively. Except for IGF2, promoter methylation levels were significantly higher in CRC compared to CRN. A three-gene panel (MGMT, RASSF1A, SEPT9) identified malignancy with 96.6% sensitivity, 74.0% specificity and 91.5 positive predictive value (area under the curve: 0.97), independently of tumor location, stage, and molecular pathway. Combined promoter methylation analysis of MGMT/RASSF1A/SEPT9 displays a better performance than currently available epigenetic-based biomarkers for CRC, providing the basis for the development of a non-invasive assay to detect CRC irrespective of the molecular pathway.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 63 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 16%
Researcher 10 16%
Student > Bachelor 7 11%
Student > Master 7 11%
Other 5 8%
Other 7 11%
Unknown 17 27%
Readers by discipline Count As %
Medicine and Dentistry 13 21%
Biochemistry, Genetics and Molecular Biology 11 17%
Agricultural and Biological Sciences 8 13%
Economics, Econometrics and Finance 2 3%
Chemistry 2 3%
Other 8 13%
Unknown 19 30%
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 28 February 2018.
All research outputs
#15,493,741
of 23,025,074 outputs
Outputs from Journal of Translational Medicine
#2,259
of 4,029 outputs
Outputs of similar age
#210,956
of 330,058 outputs
Outputs of similar age from Journal of Translational Medicine
#51
of 96 outputs
Altmetric has tracked 23,025,074 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 4,029 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one is in the 31st percentile – i.e., 31% of its peers scored the same or lower than it.
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We're also able to compare this research output to 96 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.