Research Papers:

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

S. Pamela K. Shiao _, Haiyan Xiao, Lixin Dong, Xiaoling Wang, Kebin Liu, Jinxiong She and Huidong Shi

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Oncotarget. 2018; 9:25557-25571. https://doi.org/10.18632/oncotarget.25374

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S. Pamela K. Shiao1,2,3, Haiyan Xiao1, Lixin Dong1, Xiaoling Wang2,4, Kebin Liu2,5, Jinxiong She2,3 and Huidong Shi2,5

1College of Nursing, Augusta University, Augusta, GA, USA

2Medical College of Georgia, Augusta University, Augusta, GA, USA

3Center for Biotechnology and Genomic Medicine, Augusta, GA, USA

4Georgia Prevention Institute, Augusta, GA, USA

5Georgia Cancer Center, Augusta, GA, USA

Correspondence to:

S. Pamela K. Shiao, email: [email protected]; [email protected]

Keywords: Genome wide methylation; DNA methylation regions; CRC; blood biomarkers

Received: February 20, 2018    Accepted: April 25, 2018    Published: May 22, 2018


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.

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