DNA methylation biomarkers in colorectal cancer: Clinical applications for precision medicine

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide that is attributed to gradual long‐term accumulation of both genetic and epigenetic changes. To reduce the mortality rate of CRC and to improve treatment efficacy, it will be important to develop accurate noninvasive diagnostic tests for screening, acute and personalized diagnosis. Epigenetic changes such as DNA methylation play an important role in the development and progression of CRC. Over the last decade, a panel of DNA methylation markers has been reported showing a high accuracy and reproducibility in various semi‐invasive or noninvasive biosamples. Research to obtain comprehensive panels of markers allowing a highly sensitive and differentiating diagnosis of CRC is ongoing. Moreover, the epigenetic alterations for cancer therapy, as a precision medicine strategy will increase their therapeutic potential over time. Here, we discuss the current state of DNA methylation‐based biomarkers and their impact on CRC diagnosis. We emphasize the need to further identify and stratify methylation‐biomarkers and to develop robust and effective detection methods that are applicable for a routine clinical setting of CRC diagnostics particularly at the early stage of the disease.

DNA methylation in necrotizing enterocolitis

“…Stool is utilized in biomarker studies in intestinal diseases because of the relative ease and non-invasive nature of sample acquisition; however, examining methylation patterns in stool can be technically challenging because of the abundance of bacterial DNA and the cellular degradation that occurs during passage through the intestinal tract. Despite these challenges, studies have identified altered methylation patterns in intestinal diseases such as CRC (Refs 108, 109, 110). In addition, stool DNA methylation testing in patients with IBD has been found to detect CRC and advanced precancerous lesions (Refs 111, 112).…”

DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine

“…Furthermore, combination of epigenetic therapy and immunotherapy for CRC is very promising. Candidate DNA methylation markers for prediction can reduce resistance to therapies and evaluate patient suitability for targeted therapy [ 120 ]. Epigenetic modifiers can alter the immunogenicity of the tumor microenvironment and enhance the effects of immunotherapy and immune checkpoint inhibitors [ 121 ].…”

DNA methylation biomarkers for early detection of gastric and colorectal cancers

“…To date, several potential blood-based DNA methylation biomarkers have been identified for CRC detection, including BCAT1, BMP3, C9orf50, CDKN2A, CLIP4, KCNQ5, MLH1, NDRG4, PRIMA1, SDC2, SEPT9, SFRP2 , and VIM 2 , 4 ( Table 1 ). In fact, the best-known blood epigenetic marker for CRC is SEPT9 .…”