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 Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1539
Author(s):  
Yi-Chiao Cheng ◽  
Po-Hsien Wu ◽  
Yen-Ju Chen ◽  
Cing-Han Yang ◽  
Jhen-Li Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Integrated Approach ◽  
Normal Subjects ◽  
Screening Tests ◽  
Dna Test ◽  
Crc Screening ◽  
Epigenetic Biomarkers ◽  
Novel Approach ◽  
Genome Wide

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.

scholarly journals Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chang Woo Kim ◽  
Hyunjin Kim ◽  
Hyoung Rae Kim ◽  
Bong-Hyeon Kye ◽  
Hyung Jin Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Early Detection ◽  
Prospective Trial ◽  
Screening Colonoscopy ◽  
Quantitative Detection ◽  
Screening Programs ◽  
Crc Screening ◽  
Stool Dna ◽  
Dna 2

Abstract Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer’s protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer’s instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1.

Stage-differentiated modelling of DNA methylation landscapes uncovers salient biomarkers and prognostic signatures in colorectal cancer progression

2021 ◽  
Author(s):  
Sangeetha Muthamilselvan ◽  
Abirami Raghavendran ◽  
Ashok Palaniappan
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cpg Island ◽  
Early Stage ◽  
P Value ◽  
Consensus Analysis ◽  
One Stage ◽  
Differentially Methylated Genes ◽  
Methylation Patterns ◽  
The Impact

Abstract Background: Aberrant DNA methylation acts epigenetically to skew the gene transcription rate up or down, with causative roles in the etiology of cancers. However research on the role of DNA methylation in driving the progression of cancers is limited. In this study, we have developed a comprehensive computational framework for the stage-differentiated modelling of DNA methylation landscapes in colorectal cancer (CRC), and unravelled significant stagewise signposts of CRC progression. Methods: The methylation β - matrix was derived from the public-domain TCGA data, converted into M-value matrix, annotated with AJCC stages, and analysed for stage-salient genes using multiple approaches involving stage-differentiated linear modelling of methylation patterns and/or expression patterns. Differentially methylated genes (DMGs) were identified using a contrast against controls (adjusted p-value <0.001 and |log fold-change of M-value| >2). These results were filtered using a series of all possible pairwise stage contrasts (p-value <0.05) to obtain stage-salient DMGs. These were then subjected to a consensus analysis, followed by Kaplan–Meier survival analysis to evaluate the impact of methylation patterns of consensus stage-salient biomarkers on disease prognosis.Results: We found significant genome-wide changes in methylation patterns in cancer cases relative to controls agnostic of stage. Our stage-differentiated analysis yielded the following stage-salient genes: one stage-I gene (FBN1), one stage-II gene (FOXG1), one stage-III gene (HCN1) and four stage-IV genes (NELL1, ZNF135, FAM123A, LAMA1). All the biomarkers were hypermethylated, indicating down-regulation and signifying a CpG island Methylator Phenotype (CIMP) manifestation. A significant prognostic signature consisting of FBN1 and FOXG1 survived all the steps of our analysis pipeline, and represents a novel early-stage biomarker. Conclusions: We have designed a workflow for stage-differentiated consensus analysis, and identified stage-salient diagnostic biomarkers and an early-stage prognostic biomarker panel. Our studies further yield a novel CIMP-like signature of potential clinical import underlying CRC progression.

scholarly journals Chemokines—What Is Their Role in Colorectal Cancer?

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338 ◽  
Author(s):  
Sara Pączek ◽  
Marta Łukaszewicz-Zając ◽  
Barbara Mroczko
Keyword(s):  
Colorectal Cancer ◽  
Current Knowledge ◽  
Early Stage ◽  
Distant Metastases ◽  
Cell Types ◽  
Diagnosis And Prognosis ◽  
Novel Biomarkers ◽  
Specific Receptors ◽  
Common Malignancy

Colorectal cancer (CRC) is one of the leading causes of cancer-related death. It is the second most frequently diagnosed malignancy in Europe and third worldwide. Colorectal malignancies diagnosed at an early stage offer a promising survival rate. However, advanced tumors often present distant metastases even after the complete resection of a primary tumor. Therefore, novel biomarkers of CRC are sorely needed in the diagnosis and prognosis of this common malignancy. A family of chemokines are composed of small, secreted proteins. They are best known for their ability to stimulate the migration of several cell types. Some investigations have indicated that chemokines are involved in cancer development, including CRC. This article presents current knowledge regarding chemokines and their specific receptors in CRC progression. Moreover, the prime aim of this review is to summarize the potential role of these proteins as biomarkers in the diagnosis and prognosis of CRC.

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.

Fecal DNA Testing for Colorectal Cancer Screening

2020 ◽  
Vol 71 (1) ◽  
pp. 59-69 ◽  
Author(s):  
John M. Carethers
Keyword(s):  
Colorectal Cancer ◽  
Average Risk ◽  
Fecal Dna ◽  
Polyp Detection ◽  
Serrated Polyps ◽  
Crc Screening ◽  
Epigenetic Biomarkers ◽  
Life Years ◽  
Screening Strategies ◽  
Stool Dna

Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Cross-sectional validation studies confirmed initial case-control studies’ assessment of performance of an optimized multitarget stool DNA (mt-sDNA) test, leading to approval by the US Food and Drug Administration in 2014. Compared to colonoscopy, mt-sDNA showed sensitivity of 92% for detection of CRC, much higher than the 74% sensitivity of another recommended noninvasive strategy, fecal immunochemical testing (FIT). Detections of advanced adenomas and sessile serrated polyps were higher with mt-sDNA than FIT (42% versus 24% and 42% versus 5%, respectively), but overall specificity for all lesions was lower (87% versus 95%). The mt-sDNA test increases patient life-years gained in CRC screening simulations, but its cost relative to other screening strategies needs to be reduced by 80–90% or its sensitivity for polyp detection enhanced to be cost effective. Noninvasive CRC screening strategies such as fecal DNA, however, have the potential to significantly increase national screening rates due to their noninvasive nature and convenience for patients.

scholarly journals Mapping the Colorectal Cancer Screening Scientific Landscape in South Africa: A Bibliometric Analysis to Identify Inequalities

2021 ◽  
Vol 2 (1) ◽  
pp. 27-34
Author(s):  
Magwaza S
Keyword(s):  
Colorectal Cancer ◽  
South Africa ◽  
South African ◽  
Bibliometric Analysis ◽  
Screening Colonoscopy ◽  
Scientific Publications ◽  
Crc Screening ◽  
Research Areas ◽  
Keywords Colorectal Cancer ◽  
Research Organisations

Background This paper maps scientific publications to identify areas of CRC screening that are currently receiving greatest emphasis in South African research, as means, to identify the inequality in CRC screening research. Reviewing the publications can assist to identify research funding and research capacity gaps. It can also identify potential for collaboration of authors and institutions to reduce the inequalities. Methods We used bibliometrics to identify and map the scientific publications on CRC screening related to South Africa (SA).The search utilised three databases, namely: Web of Science, Scopus and PubMed to identify articles published between January 2000 to August 2020. We identified the document by type, research areas, journal type, affiliated countries and research organisations, authors with most publications, and funding sources. Results Forty-eight of the 368 publications were included for bibliometric analysis. Of these, there were 88% original articles; 6% were reviews; 4% were books and 2% were abstracts of meetings. The top CRC screening research areas were oncology (21%); gastroenterology and hepatology (13%), public, environmental, occupational health (13%) and genetics and heredity (13%).The top four journals that have published the CRC screening related to South Africa were the South African Medical J. Surgery (10%); South African Medical Journal (7%); Clinical Genetics (5%) and Colorectal Diseases (5%). 19% of articles were published in 2019. There were 28 (58%) articles with first authors from South Africa. There were ten publications without funding declared (21%). The top five research organisations from South Africa that published the most CRC screening research were University of Witwatersrand (36%); University of Western Cape (18%); University of Pretoria (14%); University of Cape Town and KwaZulu-Natal (11%). Conclusion Research and development of novel CRC screening technologies cannot be overemphasised, as catalyst for diverse screening alternatives that are less invasive, affordable and accessible to all those in need to expand access, coverage and increase uptake at local level. Keywords: Colorectal cancer; Bibliometric; Screening; Colonoscopy; Scientific landscape; Inequalities; Cancer; South Africa.

scholarly journals Towards Novel Non-Invasive Colorectal Cancer Screening Methods: A Comprehensive Review

2021 ◽  
Author(s):  
Allegra Ferrari ◽  
Isabelle Neefs ◽  
Sarah Hoeck ◽  
Marc Peeters ◽  
Guido Van Hal
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Screening Tests ◽  
Screening Methods ◽  
Exhaled Breath ◽  
Sample Collection ◽  
Screening Programs ◽  
Crc Screening ◽  
Low Sensitivity ◽  
Standard Colonoscopy

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.

Sign in / Sign up

Export Citation Format

Share Document