Genome wide DNA differential methylation regions in colorectal cancer patients in relation to blood related family members, obese and non-obese controls - a preliminary report

Abstract

Despite evidences linking methylation changes in the cancer tissues, little is known about the methylation modification in the peripheral blood. With the current study, we identified differential methylation regions (DMRs) across human genome by collecting the blood samples of colorectal cancer (CRC) patients compared to that of their blood-related family who shared genetic inheritance and environmental influences, and unrelated obese and non-obese controls by accessing publicly available Gene Expression Omnibus data. We performed genome-wide analyses using the reduced representation bisulfite sequencing (RRBS) method covering about 25% of CpGs for whole human genome of the four groups (n = 5 each). In comparison to the non-obese controls, we observed significant DMRs in CRC for genes involved in tumorigenesis including MLH3, MSH2, MSH6, SEPT9, GNAS; and glucose transporter genes associated with obesity and diabetes including SLC2A1/GLUT1, and SLC2A3/GLUT3 that were reported on methylation being modified in cancer tissues. In addition, we observed significant DMRs in CRC for genes involved in the methylation pathways including PEMT, ALDH1L1, and DNMT3A. CRC and family members shared significant DMRs for genes of tumorigenesis including MSH2, SEPT9, GNAS, SLC2A1/GLUT1 and SLC2A3/GLUT3); and CAMK1, GLUT1/SLC2A1 and GLUT3/SLC2A3 genes involved in glucose and insulin metabolism that played vital role in development of obesity and diabetes. Our study provided evidences that these differentially methylated genes in the blood could potentially serve as candidate biomarkers for CRC diagnostic and may provide further understanding on CRC progression. Further studies are warranted to validate these methylation changes for diagnostic and prevention of CRC.

Landscape Of HOXA Genes Methylation in Colorectal Cancer

“…We observed the hypomethylation of HOXA3 and HOXA4 among our patients, which is in disagreement with other CRC studies [31,32] . It is unclear what causes the discrepancies and it will be worthwhile to reconfirm this finding in a larger cohort.…”

“…Epigenetic alteration of HOXA genes has been widely studied in many cancers, especially non-small cell lung cancer (NSCLC) [27][28][29] , yet, the investigation about this gene cluster in CRC is lacking. To date, there is only a handful of study which investigates the methylome of HOXA genes [21,[30][31][32] .…”

MiR‐4319 suppresses colorectal cancer progression by targeting ABTB1

“…3 Colorectal tumorigenesis begins with a progressive transformation of epithelial cells. 4 At the early stage, the cancer is within the mucosal layer, which is made up of epithelium, lamina propria and muscularis mucosae (stage 0-1). With the development of the CRC, tumour cells grow through or into the wall of the colon and rectum (stage 2), and spread further to the nearby lymph nodes, such as the mesenteric or inguinal lymph nodes (stage 3).…”

“…CRC mostly affects the rectum, the sigmoid colon and the distal part of the descending colon 3 . Colorectal tumorigenesis begins with a progressive transformation of epithelial cells 4 . At the early stage, the cancer is within the mucosal layer, which is made up of epithelium, lamina propria and muscularis mucosae (stage 0–1).…”