scholarly journals Serum-Based DNA Methylation Biomarkers in Colorectal Cancer: Potential for Screening and Early Detection

2013 ◽  
Vol 4 (3) ◽  
pp. 210-216 ◽  
Author(s):  
Thomas Summers ◽  
Russell C. Langan ◽  
Aviram Nissan ◽  
Björn L.D.M Brücher ◽  
Anton J. Bilchik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Early Detection

scholarly journals DNA Methylation in Colorectal cancer—Impact on Screening and Therapy Monitoring Modalities?

2007 ◽  
Vol 23 (1-2) ◽  
pp. 51-71 ◽  
Author(s):  
Marion Zitt ◽  
Matthias Zitt ◽  
Hannes M. Müller
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Therapy Monitoring ◽  
Specific Treatment ◽  
Genetic Alterations ◽  
Neoplastic Disease ◽  
Aberrant Methylation ◽  
Colon Polyps ◽  
Histological Progression

Colorectal cancer (CRC) is a common malignancy. It arises from benign neoplasms and evolves into adenocarcinomas through a stepwise histological progression sequence, proceeding from either adenomas or hyperplastic polyps/serrated adenomas. Genetic alterations have been associated with specific steps in this adenoma-carcinoma sequence and are believed to drive the histological progression of CRC. Recently, epigenetic alterations (especially DNA methylation) have been shown to occur in colon polyps and CRC. The aberrant methylation of genes appears to act together with genetic alterations to drive the initiation and progression of colon polyps to CRC.DNA methylation changes have been recognized as one of the most common molecular alterations in human tumors, including CRC. Because of the ubiquity of DNA methylation changes and the ability to detect methylated DNA in several body fluids (blood, stool), this specifically altered DNA may serve, on the one hand, as a possible new screening marker for CRC and, on the other hand, as a tool for therapy monitoring in patients having had neoplastic disease of the colorectum.As many CRC patients present with advanced disease, early detection seems to be one of the most important approaches to reduce mortality. Therefore, an effective screening test would have substantial clinical benefits. Furthermore, early detection of progression of disease in patients having had CRC permits immediate commencement of specific treatment regimens (e.g. curative resection of liver and lung metastases) and probably longer survival and better quality of life.

DNA methylation profiling from circulating tumor DNA for early-detection of colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15076-e15076
Author(s):  
Wei Zhang ◽  
Jinke Sui ◽  
Xianrui Wu ◽  
Fuao Cao ◽  
Guanyu Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Methylation Status ◽  
Stage I ◽  
Support Vector ◽  
Plasma Samples ◽  
Neoplastic Progression ◽  
Healthy Individuals ◽  
Early Stage Disease

e15076 Background: Colorectal cancer (CRC) develops as a result of neoplastic progression, which often takes decades, providing a window for early detection. Unfortunately, there has been little success in developing blood-based screening method due to the low amount of ctDNA present in the circulation, especially in patients with early stage disease. The role of aberrant DNA methylation, occurring very early in tumorigenesis, has been well elucidated. In this prospective study, we evaluated the potentiality of DNA methylation status obtained from ctDNA as an early detection method. Methods: Panel Design: Methylation data of tumor samples (12 types, n = 4,772), adjacent normal (8 types, n = 411), and normal white blood cells (n = 656) from TCGA and GSE were compared. Differentially methylated sites were extracted using modified wald-test with an adjusted p-value < 0.05 and fold-change > 2. Our panel covers 80,672 CpG sites, spanning 1.05Mb of human genome. We performed targeted bisulfite sequencing on plasma samples of 67 (stage I: 13, II:29, III: 23, IV: 2) Chinese CRC patients and 144 healthy individuals to construct a model for deriving markers that are differentially methylated and their associated weight. The model was validated in 2 independent cohorts. Results: We constructed a model using a support vector machine (SVM)-based machine learning classifier based on top 4,000 differentially methylated regions (DMRs) selected by random forest between tumor and normal plasma samples. Subsequently, 5-fold cross-validation with 100-time repeats were performed to gain a robust estimation of model performance, achieving a sensitivity of 91%, specificity of 98% and area under curve (AUC) of 98.6%. The model was subsequently validated in 2 independent cohorts: one consisted of 57 stage I-III CRC patients and 74 healthy individuals and another one with 47 stage IV patients and the same 74 healthy individuals. The model yielded a sensitivity of 83% and 95% for the early and late stage cohorts, respectively. A specificity of 95% was obtained for both cohorts. Conclusions: Our findings demonstrated the potential of profiling DNA methylation, which can effectively distinguish cancerous from healthy, for the purpose of screening. This method has potential to serve as a supplementary or alternative approach in early detection.

scholarly journals Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4965
Author(s):  
Sorina Andreea Anghel ◽  
Corina-Bianca Ioniță-Mîndrican ◽  
Ioana Luca ◽  
Anca Lucia Pop
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Current Knowledge ◽  
Early Stage ◽  
Eligibility Criteria ◽  
Mt Dna ◽  
Crc Screening ◽  
Epigenetic Biomarkers ◽  
Keywords Colorectal Cancer

In CRC, screening compliance is decreased due to the experienced discomfort associated with colonoscopy, although this method is the gold standard in terms of sensitivity and specificity. Promoter DNA methylation (hypomethylation or hypermethylation) has been linked to all CRC stages. Study objectives: to systematically review the current knowledge on approved biomarkers, reveal new potential ones, and inspect tactics that can improve performance. This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; the risk of bias was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). The Web of Science® Core Collection, MEDLINE® and Scopus® databases were searched for original articles published in peer-reviewed journals with the specific keywords “colorectal cancer”, “early detection”, “early-stage colorectal cancer”, “epigenetics”, “biomarkers”, “DNA methylation biomarkers”, “stool or blood or tissue or biopsy”, “NDRG4”, “BMP3”, “SEPT9”, and “SDC2”. Based on eligibility criteria, 74 articles were accepted for analysis. mSDC2 and mSEPT9 were frequently assessed in studies, alone or together as part of the ColoDefense panel test—the latter with the greatest performance. mBMP3 may not be an appropriate marker for detecting CRC. A panel of five methylated binding sites of the CTCF gene holds the promise for early-stage specific detection of CRC. CRC screening compliance and accuracy can be enhanced by employing a stool mt-DNA methylation test.

scholarly journals A novel cell‐free DNA methylation‐based model improves the early detection of colorectal cancer

2021 ◽  
Author(s):  
Xianrui Wu ◽  
Yunfeng Zhang ◽  
Tuo Hu ◽  
Xiaowen He ◽  
Yifeng Zou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Cell Free Dna ◽  
Free Dna
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