Shiao S Pamela K, Xiao Haiyan, Dong Lixin, Wang Xiaoling, Liu Kebin, She Jinxiong, Shi Huidong
College of Nursing, Augusta University, Augusta, GA, USA.
Medical College of Georgia, Augusta University, Augusta, GA, USA.
Oncotarget. 2018 May 22;9(39):25557-25571. doi: 10.18632/oncotarget.25374.
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 , ; and glucose transporter genes associated with obesity and diabetes including and 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 , , and . CRC and family members shared significant DMRs for genes of tumorigenesis including , ); and and 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.
尽管有证据表明癌症组织中的甲基化变化存在关联,但对于外周血中的甲基化修饰却知之甚少。在本研究中,我们通过收集结直肠癌(CRC)患者及其具有遗传和环境共同影响的血亲的血液样本,以及通过获取公开可用的基因表达综合数据库中的无关肥胖和非肥胖对照样本,来识别全人类基因组中的差异甲基化区域(DMRs)。我们使用简化代表性亚硫酸氢盐测序(RRBS)方法对四组(每组n = 5)的全人类基因组中约25%的CpG进行全基因组分析。与非肥胖对照相比,我们在CRC中观察到与肿瘤发生相关的基因(包括……;以及与肥胖和糖尿病相关的葡萄糖转运蛋白基因(包括……和……,这些基因在癌症组织中的甲基化已被报道发生改变)存在显著的DMRs。此外,我们在CRC中观察到参与甲基化途径的基因(包括……、……和……)存在显著的DMRs。CRC患者及其家庭成员在与肿瘤发生相关的基因(包括……、……);以及参与葡萄糖和胰岛素代谢且在肥胖和糖尿病发展中起关键作用的……和……基因方面共享显著的DMRs。我们的研究提供了证据,表明血液中这些差异甲基化基因可能潜在地作为CRC诊断的候选生物标志物,并可能为CRC进展提供进一步的理解。有必要进行进一步的研究来验证这些甲基化变化用于CRC的诊断和预防。