DNA methylation markers detected in blood, stool, urine, and tissue in colorectal cancer: a systematic review of paired samples

Abstract

Purpose Methylated cell-free DNA in liquid biopsies are promising non-invasive biomarkers for colorectal cancer (CRC). Optimal markers would have high sensitivity and specificity for early detection of CRC and could be detected in more than one type of material from the patient. We systematically reviewed the literature on DNA methylation markers of colorectal cancer, detected in more than one type of material, regarding their potential as contributors to a panel for screening and follow-up of CRC. Methods The databases MEDLINE, Web of Science, and Embase were systematically searched. Data extraction and review was performed by two authors independently. Agreement between methylation status in tissue and other materials (blood/stool/urine) was analyzed using the McNemar test and Cohen’s kappa. Results From the 51 included studies, we identified seven single markers with sensitivity ≥ 75% and specificity ≥ 90% for CRC. We also identified one promising plasma panel and two stool panels. The correspondence of methylation status was evaluated as very good for four markers, but only marginal for most of the other markers investigated (12 of 21). Conclusion The included studies reported only some of the variables and markers of interest and included few patients. Hence, a meta-analysis was not possible at this point. Larger, prospective studies must be designed to study the discordant detection of markers in tissue and liquid biopsies. When reporting their findings, such studies should use a standardized format.

Liquid biopsies and cancer omics

“…Saliva, urines, seminal fluids, tears, and stool have been analyzed to understand their correlation with cancer 36 . Stool in particular have been thoroughly evaluated in the context of gastrointestinal cancers, and proved to be a valuable source of tumoral DNA for pancreatic cancer [37][38][39][40] . Stool analysis from a multiomics perspective is also able to integrate information on the role of the microbiome in cancer pathogenesis, especially in the case of colorectal cancer and pancreatic cancer, as well as in other disease entities such as inflammatory intestinal diseases [41][42][43] .…”

Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer

“…DNA methylation is one of the most important and earliest epigenetic hallmarks of CRC [ 133 ]. Up to now, clinical studies have shown that the methylated epigenetic ctDNA markers serve as promising candidates for CRC screening modality in serum/plasma of CRC patients [ 134 ]. A study by Young et al, designed a multi-panel methylation assay for detection of specific methylation markers, Branched Chain Amino Acid Transaminase 1(BCAT1), IKAROS Family Zinc Finger 1I(KZF1) and Interferon Regulatory Factor 4 (IRF4), in plasma of CRC patients.…”

Sampling, Logistics, and Analytics of Urine for RT-qPCR-based Diagnostics

“…In the field of cancer diagnostics, non-invasive technologies are increasingly attractive for initial diagnosis of tumors and for therapy monitoring [1][2][3]. Body fluids are the primary source of liquid biopsy, i.e., biomarker detection, and include blood and serum, urine, and saliva [4,5].…”