Noninvasive DNA methylation biomarkers in colorectal cancer: A systematic review

Xue, Min; Lai, Shih-Kung; Xu, Zhi Peng; Wang, Liang Jing

doi:10.1111/1751-2980.12299

Cited by 16 publications

(9 citation statements)

References 94 publications

(398 reference statements)

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“…While the latter one is expected for molecules with antioxidant properties, the others represent a very interesting finding, in consideration that a large number of anticancer drugs are targeted to nucleotide metabolism enzymes20. Moreover, methylation/demethylation processes are of extreme relevance in gene regulation, and involved in various processes of cancer development and progression21, also in colorectal cancer22. Indeed epigenetic drugs such as azacytidine, its deoxy derivative 5-aza-2′-deoxycytidine (decitabine) and hydralazine have been developed to act as inhibitors of DNA methyltransferases involved in epigenetic regulation phenomena and are currently used in the treatment of myelodysplastic syndromes, but their severe side effects discourage their use in other tumors23.…”

Section: Resultsmentioning

confidence: 99%

A theoretical study on predicted protein targets of apple polyphenols and possible mechanisms of chemoprevention in colorectal cancer

Scafuri

Marabotti

Carbone

et al. 2016

Sci Rep

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We investigated the potential role of apple phenolic compounds in human pathologies by integrating chemical characterization of phenolic compounds in three apple varieties, computational approaches to identify potential protein targets of the compounds, bioinformatics analyses on data from public archive of gene expression data, and functional analyses to hypothesize the effects of the selected compounds in molecular pathways. Starting by the analytic characterization of phenolic compounds in three apple varieties, i.e. Annurca, Red Delicious, and Golden Delicious, we used computational approaches to verify by reverse docking the potential protein targets of the identified compounds. Direct docking validation of the potential protein-ligand interactions has generated a short list of human proteins potentially bound by the apple phenolic compounds. By considering the known chemo-preventive role of apple antioxidants’ extracts against some human pathologies, we performed a functional analysis by comparison with experimental gene expression data and interaction networks, obtained from public repositories. The results suggest the hypothesis that chemo-preventive effects of apple extracts in human pathologies, in particular for colorectal cancer, may be the interference with the activity of nucleotide metabolism and methylation enzymes, similarly to some classes of anticancer drugs.

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Section: Resultsmentioning

confidence: 99%

A theoretical study on predicted protein targets of apple polyphenols and possible mechanisms of chemoprevention in colorectal cancer

Scafuri

Marabotti

Carbone

et al. 2016

Sci Rep

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“…Notably, it has been stated that detection of DNA methylation biomarkers for CRC alone or in combination with other markers improved the cancer detection sensitivity …”

Section: Discussionmentioning

confidence: 99%

Study of p16 promoter methylation in Egyptian colorectal cancer patients

Karam

Zidan

Elrahman

et al. 2018

J of Cellular Biochemistry

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Many tumor‐suppressor genes contain CpG islands in their promoter regions which raised the necessity of investigating the role of methylation in silencing these genes. We examined p16 methylation as a potential biomarker in the peripheral blood of colorectal cancer (CRC) patients. Using methylation‐specific polymerase chain reaction method, the methylation status of p16 was investigated in the tumor tissue and blood of 65 CRC patients and blood samples from 70 healthy control individuals. Also, the relationship between p16 methylation level and the clinical‐pathological findings in CRC was evaluated. The frequency of blood p16 methylation in CRC cases was significantly higher than in control (P = 0.0001). The sensitivity and specificity of p16 methylation in diagnosing CRC was 55.38% and 98.5%, respectively, with 77.7% diagnostic accuracy. There was significant association between p16 methylation and age, sex, Dukes staging, lymph node involvement, and carcinoembryonic antigen levels. Our study revealed that p16 promoter methylation could be considered as both potential diagnostic and prognostic biomarker of CRC.

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“…Based on their low background in plasma of normal subjects, 3.5%, 6.8%, 4.9% and 4.2% respectively, the four genes BCAT1 , GRASP , IKZF1 and IRF4 were considered suitable for assay development and optimization. Xue et al [37] have recently reviewed studies evaluating blood-based detection of DNA methylation biomarkers for colorectal cancer and the above represent promising biomarkers that could be combined with these or other markers to potentially provide improved sensitivity for cancer detection. In combining biomarkers to improve assay sensitivity, it is critical that individual markers have minimal false positive detection rates in normal subjects in order to maintain good specificity.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer

Mitchell

Brown

et al. 2016

Genes

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Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA. We have used a novel approach for assessment of low levels of DNA methylation in WBC DNA. DNA methylation in 29 previously identified regions (residing in 17 genes) was analyzed in WBC DNA and eight differentially-methylated regions (DMRs) were taken through to testing in clinical samples using methylation specific PCR assays. DMRs residing in four genes, BCAT1, GRASP, IKZF1 and IRF4, exhibited low positivity, 3.5% to 7%, in the plasma of colonoscopy-confirmed healthy subjects, with the sensitivity for detection of ctDNA in colonoscopy-confirmed patients with colorectal cancer being 65%, 54.5%, 67.6% and 59% respectively.

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Noninvasive DNA methylation biomarkers in colorectal cancer: A systematic review

Abstract: Genetic markers might be minimally invasive, economical and accurate for the screening and surveillance of CRC. Large multicenter studies evaluating these biomarkers systematically and prospectively not only in CRC but also in other types of cancers are needed in the future.

Cited by 16 publications

References 94 publications

A theoretical study on predicted protein targets of apple polyphenols and possible mechanisms of chemoprevention in colorectal cancer

A theoretical study on predicted protein targets of apple polyphenols and possible mechanisms of chemoprevention in colorectal cancer

Study of p16 promoter methylation in Egyptian colorectal cancer patients

Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer

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