DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps

Abstract

Colorectal cancer (CRC) screening rates are currently suboptimal. Blood-based screening could improve rates of earlier detection for CRC and adenomatous colorectal polyps. In this study, we evaluated the feasibility of plasma-based detection of early CRC and adenomatous polyps using array-mediated analysis methylation profiling of 56 genes implicated in carcinogenesis. Methylation of 56 genes in patients with stage I and II CRC (N=30) and those with adenomatous polyps (N=30) were compared to individuals who underwent colonoscopy and were found to have neither adenomatous changes nor CRC. Composite biomarkers were developed for adenomatous polyps and CRC, and their sensitivity and specificity was estimated using five-fold cross validation. Six promoters (CYCD2, HIC1, PAX 5, RASSF1A, RB1, and SRBC) were selected for the biomarker, which differentiated CRC patients and controls with 84% sensitivity and 68% specificity. Three promoters (HIC1, MDG1, and RASSF1A) were selected for the biomarker, which differentiated patients with adenomatous polyps and controls with sensitivity of 55% and specificity of 65%. Methylation profiling of plasma DNA can detect early CRC with significant accuracy and shows promise as a methodology to develop biomarkers for CRC screening.

Future perspectives of circulating tumor DNA in colorectal cancer

“…51,73,74 Promising results have also been reported using multigene methylation signatures for CRC screening in order to increase sensitivity and specificity. [61][62][63][64][65][66][67][68][69] For example, an approach using a BCAT1 and IKZF1 methylation assay identified approximately 70% of CRC. [75][76][77] Detection of tumor recurrence, minimal residual disease, and prognosis value Surgery alone cures a large fraction of patients with localized CRC.…”

DNA Methylation in Whole Blood: Uses and Challenges

“…In a candidate gene study, Cassinotti et al (2012) analyzed whole blood from 30 colorectal cancer (CRC) patients, 30 patients with adenomatous polyps, and 30 controls [9]. Samples were digested with the restriction enzyme Hin6I, and PCR was used to measure DNA methylation at loci mapped to 56 genes.…”

“…Because access to blood specimens is typically much more convenient to obtain from human subjects, the bulk of published studies have used whole blood (sometimes referred to as peripheral blood). A wide variety of phenotypes and health conditions have been studied: aging [4][5][6][7][8], cancer [9][10][11][12], obesity [5,13], cardiovascular disease [14], prenatal exposures/perinatal outcomes [15,16], environmental exposures [17][18][19][20][21][22][23][24] (tobacco in particular [25,26]), inflammatory diseases [27, 28•], psychiatric conditions [21,[29][30][31][32], and fertility [33]. While many of these studies have used candidate gene approaches with bisulfite-pyrosequencing, an increasing number have conducted epigenome-wide association studies (EWAS) using commercially available microarrays such as the Infinium HumanMethylation450 BeadChip assay ("450K," produced by Illumina, Inc.), its predecessor, the Infinium HumanMethylation27 BeadChip ("27K"), or an This article is part of the Topical Collection on Environmental Epigenetics older Illumina product based on the company's GoldenGate product.…”

Biomarkers for Early Detection of Colorectal Cancer and Polyps: Systematic Review

“…Blood samples were analyzed for epigenetic changes of genes involved in the tumor progression sequence. Four of these papers (38,40,41,43) (Continued on the following page) Table 2. Table 2.…”