Detection of DNA hypermethylation in remote media of patients with colorectal cancer: new biomarkers for colorectal carcinoma

Abstract

Colorectal cancer is the third most common cancer and a major cause of cancer-related mortality. The lifetime risk to develop colorectal cancer is 6% in the Western world, and one third of the affected people will ultimately die from this disease. Colorectal carcinomas develop slowly over a period of several years. Therefore, identifying people with precancerous lesions holds the potential to reduce the incidence and mortality of colorectal cancer. Apart from mutations and chromosomal imbalances, inactivation of tumor suppressor genes by DNA hypermethylation has been recognized as an important mechanism driving colorectal carcinogenesis. In recent years, screening tests have been developed that rely on the detection of DNA hypermethylation in remote media to identify people suffering from asymptomatic colorectal cancers at early stages. Apart from their diagnostic value, methylation markers hold the potential to be used as prognostic markers. Here, we summarize the recent development of DNA methylation markers for colorectal cancer in remote media with regard to their diagnostic and prognostic value.

Circulating cell-free methylated DNA and lactate dehydrogenase release in colorectal cancer

“…Genes found hypermethylated in colorectal cancer have many functions, including mismatch repair, cell-cycle regulation and cell differentiation [4]. Methylated tumor DNA cannot only be found in primary colorectal cancer tissue, but can also be detected in remote media like serum or stool and potentially be used as biomarkers for various purposes [5-7]. We have previously described methylation of the genes neurogenin 1 (NEUROG1) in serum and HIC1 in stool as diagnostic markers [8,9] and helicase-like transcription factor (HLTF) and hyperplastic polyposis 1 (HPP1) , also known as transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFF2) , as prognostic serum markers [10,11].…”

Diagnostic Performance of DNA Hypermethylation Markers in Peripheral Blood for the Detection of Colorectal Cancer: A Meta-Analysis and Systematic Review

“…The detection of aberrantly methylated septin 9 ( SEPT9 ) in plasma may be a valuable and non-invasive blood-based polymerase chain reaction (PCR) test, with almost 70% sensitivity and 90% specificity for detection of CRC[ 13 – 16 ]. The utility of methylation for CRC detection has been reported for an increasing number of genes, including THBD , NEUROG1 , HIC1 , DAPK , APC , MDG1 , and TPEF [ 17 – 21 ].…”

Noninvasive DNA methylation biomarkers in colorectal cancer: A systematic review

“…A cluster of genes characterized by altered DNA methylation have been identified during the past few decades along these chromosomes, including Zinc finger of the cerebellum 1 ( ZIC1 ) and Klotho ( KL ), which were first found to be hypermethylated in CRC in our previous studies . Methylated DNA fragments are detectable in not only primary tumor tissues but also remote media including blood, stool, urine and bowel lavage fluid, making them eligible to act as a screening tool for CRC in clinical setting. In this review, we aimed to summarize the current evidence on the biomarkers associated with DNA methylation in the screening and diagnosis of CRC.…”