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

Abstract

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.

State-of-the-Art Review on Immersive Virtual Reality Interventions for Colonoscopy-Induced Anxiety and Pain

“…It, therefore, may remain a primary screening procedure for CRC. However, other research directions pursue raising sensitivity and specificity of currently available alternative screening procedures, such as the imagistic analysis [ 8 ], epigenetic faecal biomarkers [ 9 ], urine, and exhaled breath or blood-based biomarkers [ 10 ]. In Europe, Colon Capsule Endoscopy is currently considered acceptable as a screening method regarding specificity and sensitivity.…”

Combined Efficacy of CXCL5, STC2, and CHI3L1 in the Diagnosis of Colorectal Cancer

“…Another promising epigenetic biomarker is the SDC2 (Syndecan-2) gene methylation in the stool. Sensitivities of m SDC2 for stages I/II were between 83.3 and 91.4%, and 89.6 and 100% for stage III/IV [8]. Although these improvements (in comparison with CEA) were significant, two shortcomings would limit the clinical popularization and promotion.…”

“…e emerging epigenetic biomarkers [6], such as methylated septin9 and SDC2 (syndecan-2) genes, have been entered into clinical practice with a considerable improvement of diagnostic accuracy [7,8].…”

Short-chain fatty acid concentrations in the incidence and risk-stratification of colorectal cancer: a systematic review and meta-analysis

“…The guaiac fecal occult blood test (gFOBT) and fecal immunochemical test (FIT) are other, in practice, non-invasive stool-based methods for CRC screening, which however require improvement, in particular for detection of CRA or early-stage colonic carcinogenesis (Ferrari et al 2021;Imperiale et al 2019;Jodal et al 2019). Fecal SCFA could be considered as a potential non-invasive biomarker to be measured in combination with or as an alternative to the commonly used non-invasive and current CRC screening methods (Anghel et al 2021;Ferrari et al 2021), to improve specificity and sensitivity of current screening, as well as for potential early detection of CRA.…”

“…2019). Fecal SCFA could be considered as a potential non-invasive biomarker to be measured in combination with or as an alternative to the commonly used non-invasive and current CRC screening methods (Anghel et al . 2021; Ferrari et al .…”