Dataset Information

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

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Freitas M

PROVIDER: S-EPMC6389195 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Freitas Micaela M Ferreira Fábio F Carvalho Sónia S Silva Fernanda F Lopes Paula P Antunes Luís L Salta Sofia S Diniz Francisca F Santos Lúcio Lara LL Videira José Flávio JF Henrique Rui R Jerónimo Carmen C

Journal of translational medicine 20180227 1

<h4>Background</h4>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 advant ...[more]

PMID: 29486770

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Project description:Objectives: Early identification of smoking, essential for the successful implementation of interventions, arrests the escalation of smoking and smoking-associated risk behaviors in adolescents. However, because nascent smoking is typically episodic and infrequent, enzyme-linked immunoassay reagent-based approaches that detect cotinine, a key nicotine metabolite, are not effective in identifying adolescents in the earliest stages of smoking. Epigenetic methods may offer an alternative approach for detecting early-stage smokers. In prior work, we and others have shown that the methylation status of cg05575921 of whole-blood DNA accurately predicts smoking status in regularly smoking adults and is sensitive to nascent smoking. Yet, the blood draws necessary to obtain DNA for this method may be poorly accepted by adolescents. Saliva could be an alternative source of DNA. However, the ability of saliva DNA methylation status to predict smoking status among adolescents is unknown. Methods: To explore the possibility of using salivary DNA for screening purposes, we examined the DNA methylation status at cg05575921 in saliva DNA samples from 162 high school aged subjects for whom we also had paired serum cotinine values. Results: Overall, the reliability of self-report of nicotine/tobacco use in these adolescents was poor with 67% of all subjects whose serum levels of cotinine was ?2?ng/mL (n?=?75) denying any use of nicotine-containing products in the past 6 months. However, the correspondence of the two biological measures of smoking was high, with serum cotinine positivity being strongly correlated with cg05575921 methylation (p?<?0.0001). Receiver operating characteristic (ROC) analyses showed that cg05575921 methylation status could be used to classify those with positive serum cotinine values (?2?ng/mL) from those denying smoking and have undetectable levels of cotinine. Conclusions: We conclude that saliva DNA methylation assessments hold promise as a means of detecting nascent smoking.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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