scholarly journals Genome-Wide Open Chromatin Methylome Profiles in Colorectal Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 719
Author(s):  
Muhiddin Ishak ◽  
Rashidah Baharudin ◽  
Isa Mohamed Rose ◽  
Ismail Sagap ◽  
Luqman Mazlan ◽  
...  

The methylome of open chromatins was investigated in colorectal cancer (CRC) to explore cancer-specific methylation and potential biomarkers. Epigenome-wide methylome of open chromatins was studied in colorectal cancer tissues using the Infinium DNA MethylationEPIC assay. Differentially methylated regions were identified using the ChAMP Bioconductor. Our stringent analysis led to the discovery of 2187 significant differentially methylated open chromatins in CRCs. More hypomethylated probes were observed and the trend was similar across all chromosomes. The majority of hyper- and hypomethylated probes in open chromatin were in chromosome 1. Our unsupervised hierarchical clustering analysis showed that 40 significant differentially methylated open chromatins were able to segregate CRC from normal colonic tissues. Receiver operating characteristic analyses from the top 40 probes revealed several significant, highly discriminative, specific and sensitive probes such as OPLAH cg26256223, EYA4 cg01328892, and CCNA1 cg11513637, among others. OPLAH cg26256223 hypermethylation is associated with reduced gene expression in the CRC. This study reports many open chromatin loci with novel differential methylation statuses, some of which with the potential as candidate markers for diagnostic purposes.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qing-Lan Li ◽  
Xiang Lin ◽  
Ya-Li Yu ◽  
Lin Chen ◽  
Qi-Xin Hu ◽  
...  

AbstractColorectal cancer is one of the most common cancers in the world. Although genomic mutations and single nucleotide polymorphisms have been extensively studied, the epigenomic status in colorectal cancer patient tissues remains elusive. Here, together with genomic and transcriptomic analysis, we use ChIP-Seq to profile active enhancers at the genome wide level in colorectal cancer paired patient tissues (tumor and adjacent tissues from the same patients). In total, we sequence 73 pairs of colorectal cancer tissues and generate 147 H3K27ac ChIP-Seq, 144 RNA-Seq, 147 whole genome sequencing and 86 H3K4me3 ChIP-Seq samples. Our analysis identifies 5590 gain and 1100 lost variant enhancer loci in colorectal cancer, and 334 gain and 121 lost variant super enhancer loci. Multiple key transcription factors in colorectal cancer are predicted with motif analysis and core regulatory circuitry analysis. Further experiments verify the function of the super enhancers governing PHF19 and TBC1D16 in regulating colorectal cancer tumorigenesis, and KLF3 is identified as an oncogenic transcription factor in colorectal cancer. Taken together, our work provides an important epigenomic resource and functional factors for epigenetic studies in colorectal cancer.


PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e92553 ◽  
Author(s):  
Nur Zarina Ali Hassan ◽  
Norfilza Mohd Mokhtar ◽  
Teow Kok Sin ◽  
Isa Mohamed Rose ◽  
Ismail Sagap ◽  
...  

2020 ◽  
Author(s):  
Xiao-liang Xing ◽  
Zhi-Yong Yao ◽  
Ti Zhang ◽  
Ning Zhu ◽  
Xingyu Liu ◽  
...  

Abstract BackgroundColorectal cancer (CRC) is the third most common cancer which could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) mainly. Accumulating evidence indicatedmethylations are involved in multiple tumors.MethodsTo know the effect of abnormal methylation in COAD, READ and CRC, we downloaded methylation and mRNA data of COAD and READ from The Cancer Genome Atlas (TCGA) database. And then, we used DESeq2, ChAMP, DAVID 6.8, Cytoscape_3.7.2 and Correlation analysis to identify the potential biomarkers.ResultsWe obtain 12 potential biomarkers (APBB1, CDC42SE2, EIF4E3, FBXO17, FES, GNPNAT1, HSPA1A, OSBPL3, RORC, SALL1, SPEG, and TCF7L1) directly associated with the pathologic TNM of COAD maybe regulated by 28 differential methylations; 2 potential biomarkers (AQP1 and HOXA3) directly associated with pathologic NM maybe regulated by 8 differential methylations; and 15 potential biomarkers (ADAMTSL3, ANXA9, APBB1, AQP1, C2CD4A, CLIP3, DNAJC15, EIF4E3, FAM160A1, GNG4, HLX, HSPA1A, LAYN, NR3C2, and SYT1)directly associated with the pathologic TNM of COAD maybe regulated by 29 differential methylations. Furthermore, weconstruct the network of differential methylation and differential expression genes. In addition, we also obtain 1 methylation (cg18149207), 2 methylations (cg02000808 and cg21134232) and 2 methylations (cg04408595 and cg19413725) associated with the overall survival.ConclusionOur results provide an analysis of theoretical knowledge and clinical outcomes, but more researches are needed to confirm our findings.


Epigenomics ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1765-1778
Author(s):  
Sonja Neumeyer ◽  
Odilia Popanda ◽  
Katja Butterbach ◽  
Dominic Edelmann ◽  
Hendrik Bläker ◽  
...  

Aim: Use of menopausal hormone therapy (MHT) has been associated with a reduced risk for colorectal cancer, but mechanisms underlying this relationship are not well understood. In the colon, MHT appears to act through estrogen receptor β (ERβ) which may influence DNA methylation by binding to DNA. Using genome-wide methylation profiling data, we aimed to identify genes that may be differentially methylated according to MHT use. Materials & methods: DNA methylation was measured using Illumina HumanMethylation450k arrays in two independent tumor sample sets of colorectal cancer patients. Differential methylation was determined using R/limma. Results: In the discovery analysis, two CpG sites showed differential DNA methylation according to MHT use, both were not replicated. In stratified analyses, 342 CpG sites were associated with current MHT use only in ERβ-positive tumors. Conclusion: The suggestive findings of differential methylation according to current MHT use in ERβ-positive tumors warrant further investigation.


2016 ◽  
Vol 5 (7) ◽  
pp. 1629-1639 ◽  
Author(s):  
Dong Chen ◽  
Qiang Sun ◽  
Xiaofei Cheng ◽  
Lufei Zhang ◽  
Wei Song ◽  
...  

2021 ◽  
Author(s):  
Xin Zhang ◽  
Tao Li ◽  
Qiang Niu ◽  
Chang Jiang Qin ◽  
Ming Zhang ◽  
...  

Abstract Background: To verify the feasibility of genome-wide plasma cell-free DNA(cfDNA) methylation profiling for early diagnosis of colorectal cancer.Methods: We performed a genome-wide cfDNA methylation profiling study of colorectal cancer patients by methylated DNA immunoprecipitation coupled with high throughput sequencing (MeDIP-seq).Results: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients, 16 of these DMRs were hypermethylated and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly including PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data.Conclusions: Our study indicates that MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and the differentially methylated genes obtained by MeDIP-seq can be used as potential biomarkers for clinical application in patients with colorectal cancer.


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