DNA hypermethylation in colorectal cancer: Colorectal cancer tissues vs. Adjacent non-tumor tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Hong Weiguo
PROVIDER: E-GEOD-33545 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:To identify novel hypermethylated genes in colorectal cancer (CRC) and to test their potential application in CRC early diagnosis, we performed a genome-wide screening of 57,723 CpG dinucleotides covering 4,010 genes in paired DNA samples extracted from 3 fresh frozen CRC tissues and their matching non-tumor adjacent tissues from a cohort of 3 CRC patients undergoing curative surgery using MIRA-based microarray. We also validated candidate hypermethylated genes screened by MIRA-based microarray in independent CRC samples using combined bisulfite restriction analysis. A total of 297 CpG dinucleotides in CRC covering 211 genes were found to be hypermethylated in CRC tissues. From these 211 candidate methylated genes, seven novel methylated genes were picked up for validation and three genes were confirmed to be methylated in cancer samples but not in non-cancer samples.We also compared the methylation levels of these three novel hypermethylated genes with those of Vimentin and SEPT9, well-known hypermethylated genes in CRC, and found that methylated PHOX2B, FGF12 and GAD2 were better than methylated Vimentin and SEPT9 in differentiating CRC cancer tissue from normal tissue. Significant enrichment analysis of GO terms of the hypermethylated genes showed that a high proportion of hypermethylated genes in tumor tissues are involved in regulation of transcription.
2011-11-14 | GSE33545 | GEO
Project description:Determination of the profile of genes commonly aberrantly methylated in colorectal cancer (CRC) has substantial potential value for diagnostic and therapeutic application. However, our knowledge of the DNA methylation pattern in CRC is currently limited. Therefore, we analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in adjacent normal mucosa using beadchip array-based technology. We identified 621 CpG sites located in promoter region and CpG islands that were significantly hypermethylated in CRC compared to normal mucosa. Genes on chromosome 18 showed promoter hypermethylation most frequently. According to gene ontology analysis, the most common biologically relevant class of genes affected by methylation was the class associated with the cadherin signaling pathway. In comparison with genome-wide expression array, mRNA expression was more like to be down-regulated in the genes demonstrating promoter hypermethylation, although this was not statistically significant. We validated 10 CpG sites that were shown to be hypermethylated in the array studies (ADHFE1, BOLL, SLC6A15, ADAMTS5, TFPI2, EYA4, NPY, TWIST1, LAMA1, GAS7) and 2 CpG sites showing hypomethylaion (MAEL, SFT2D3) in CRC compared to normal mucosa using pyrosequencing. The methylation status measured by pyrosequencing was consistent with the methylation array data. In conclusion, we have shown that methylation profiling based on beadchip arrays is an effective method for screening for aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC. We measured the methylation status of the 27,578 CpG sites (Human Methylation27 DNA Analysis BeadChip) in 22 pairs of CRC tissue and adjacent normal mucosa to identify genes that are commonly aberrantly methylated in CRC.
2010-06-24 | E-GEOD-17648 | biostudies-arrayexpress
Project description:Methylated genomic fragments from tumor DNA and matching normal control were enriched with the methylated-CpG island recovery assay (MIRA); amplified, labeled and hybridized on Agilent CpG island tiling oligo arrays. MIRA enriched samples from tumor were labeled with Cy5 while MIRA enriched DNA samples from normal tissue were labeled with Cy3. Keywords: Cancer
2009-02-18 | GSE14865 | GEO
Project description:Background: Colorectal cancer (CRC) remains a major concern with high morbidity and mortality worldwide. DNA methylation alteration plays a pivotal role in cancer development. We aimed to screen novel biomarkers for CRC diagnosis and chemotherapy-related adverse event (CRAE) prediction using the advanced Illumina Infinium MethylationEPIC (850K) BeadChip. Methods: We analyzed the methylation profiles of paired tumor and normal tissues from 21 Chinese CRC patients. After normalization by potential confounders, three types of methylation profiles (differentially methylated probes, differentially methylated regions, and gene-function-differentially methylated regions) were further studied by functional annotation and pathway enrichment analysis. At last, integrated-methylation-marker systems for CRC diagnosis and CRAE prediction were developed based on genes within the mostly related pathways and LASSO regression. Findings: Tumor-related methylation was characterized with hypermethylated promoter islands and hypomethylated intragenic openseas. CRAE-related methylation was characterized with hyper- (or hypo-) methylated intragenic (or intergenic) regions. The two most important susceptible factors for various types of CARE were inactive regeneration functions and active immune response. Differentially methylated genes were significantly enriched in neuronal system, metabolism of RNA, and extracellular matrix organization. All of the integrated-methylation-marker systems demonstrated high discriminative accuracy in both CRC diagnosis (AUROC = 1) and CRAE prediction (AUROC = 0.817-1). Interpretation: In this study, we provided new insights on the formation of CRC diagnosis and CRAE based on three types of methylation profile. The integrated-methylation-marker systems combining multiple DMPs were found to have potentially diagnostic and predictive values. Hence, our findings have important clinical implications, and further validation is warranted.
2021-08-01 | GSE159898 | GEO
Project description:Background an Aim: Epigenetics are thought to play a major role in the carcinogenesis of patients that develop multiple colorectal cancers (CRC) in the non-hereditary setting. Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the underlying epigenetic signature that differentiates multiple from solitary colorectal cancer tumors using a genome-scale DNA methylation profiling. Patients and Methods: We used a population-based cohort (EPICOLON II) of 12 patients with synchronous CRC and 29 age- sex- and tumor location-paired solitary CRC patients. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significantly hypermethylated CpG sites results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP) using the Infinium DNA methylation data; KRAS and BRAF mutations; microsatellite instability; and immunohistochemistry for MLH1/MSH2/MSH6/PMS2. Functional annotation clustering of differentially methylated genes between multiple and solitary CRCs was performed. Results: We identified 102 CpG sites that showed significant DNA hypermethylation in multiple versus solitary tumors (difference in M-NM-2 value >0.1 and p<0.05). Methylight assays validated the array results for 4 selected significantly hypermethylated genes (MAP1B, HTRA1, ALOX15, TIMP3) identified in the profiling (p=0.0002). Based on the Infinium data, 8/12 (66.6%) of multiple tumors were classified as CIMP-high, as compared to 5/29 (17%) solitary tumors (p=0.004). CIMP-high tumors displayed significant hypermethylation in 301 CpG sites (difference in M-NM-2 value >0.1; p value <0.05). Interestingly, 76/102 (74.5%) of the hypermethylated CpG sites found in multiple vs. solitary tumors were also seen to be hypermethylated in CIMP-H tumors. Functional analysis of hypermethylated genes found in multiple vs. solitary tumors showed the presence and enrichment of genes involved in different tumorigenic functions. Conclusions: Multiple colorectal cancers are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity in the non-hereditary scenario, and provide novel potential biomarkers for identifying high-risk patients and tailoring surveillance strategies. We used a population-based cohort (EPICOLON II) of 12 patients with synchronous CRC and 29 solitary CRC patients. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay.
2014-09-01 | E-GEOD-52573 | biostudies-arrayexpress
Project description:Determination of the profile of genes commonly aberrantly methylated in colorectal cancer (CRC) has substantial potential value for diagnostic and therapeutic application. However, our knowledge of the DNA methylation pattern in CRC is currently limited. Therefore, we analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in adjacent normal mucosa using beadchip array-based technology. We identified 621 CpG sites located in promoter region and CpG islands that were significantly hypermethylated in CRC compared to normal mucosa. Genes on chromosome 18 showed promoter hypermethylation most frequently. According to gene ontology analysis, the most common biologically relevant class of genes affected by methylation was the class associated with the cadherin signaling pathway. In comparison with genome-wide expression array, mRNA expression was more like to be down-regulated in the genes demonstrating promoter hypermethylation, although this was not statistically significant. We validated 10 CpG sites that were shown to be hypermethylated in the array studies (ADHFE1, BOLL, SLC6A15, ADAMTS5, TFPI2, EYA4, NPY, TWIST1, LAMA1, GAS7) and 2 CpG sites showing hypomethylaion (MAEL, SFT2D3) in CRC compared to normal mucosa using pyrosequencing. The methylation status measured by pyrosequencing was consistent with the methylation array data. In conclusion, we have shown that methylation profiling based on beadchip arrays is an effective method for screening for aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC.
2009-08-18 | GSE17648 | GEO
Project description:Methylated genomic fragments from tumor DNA and matching normal control were enriched with the methylated-CpG island recovery assay (MIRA); amplified, labeled and hybridized on Agilent CpG island tiling oligo arrays. MIRA enriched samples from tumor were labeled with Cy5 while MIRA enriched DNA samples from normal tissue were labeled with Cy3. Keywords: Cancer Methylation patterns of tumors; six patients with early stage breast cancer (DCIS)
2010-05-05 | E-GEOD-14865 | biostudies-arrayexpress
Project description:In our study we applied a genome-wide DNA methylation analysis approach, MethylCap-seq, to map the differentially methylated regions in 24 tumor and matched normal colon samples. In total, 2687 frequently hypermethylated and 468 frequently hypomethylated regions were identified, which include potential biomarkers for CRC diagnosis. Hypermethylation in the tumor samples was enriched at CpG islands and gene promoters, while hypomethylation was distributed throughout the genome. Using epigenetic data from human embryonic stem cells, we show that frequent differentially methylated regions (DMRs) coincide with bivalent loci in human embryonic stem cells. DNA methylation is commonly thought to lead to cancer gene related silencing, however integration of publically available expression analysis shows that 75% of the frequently hypermethylation genes were most likely already lowly or not expressed in normal tissue. Collectively, our study provides genome-wide DNA methylation maps of colon cancer, comprehensive lists of DMRs, and gives further clues on the role of aberrant DNA methylation in CRC formation. To investigate DNA methylation in CRC in a genome-wide unbiased fashion, we applied MethylCap-seq. This method involves capture of methylated DNA using the MBD domain of MeCP2, and subsequent next-generation Illumina sequencing of eluted DNA. In addition, we compared MethylCap with RNA-seq and ChIP-seq profiles of H3K4me3 and H3K27me3 for the colon cancer tumor cell line HCT116 (HCT116 WT) and the cell line of HCT116 with DNMT1 and DNMT3b knockout (HCT116 DKO).
2012-10-26 | E-GEOD-39068 | biostudies-arrayexpress
Project description:Unearthing of silenced genes in colorectal cancer (CRC) is of great importance. We employed oligonucleotide microarray to find changes in global gene expression of five CRC cell lines. These were analyzed before and after treatment with the 5-aza-2'-Deoxycitidine. Expression of the responding genes was integrated with gene expression profiling generated by microarray analysis of matched colorectal tissue samples. Selected candidates were subjected to methylation-specific PCR (MSP) and real-time quantitative reverse transcription-PCR using CRC cell lines and paired tumor and normal samples from CRC patients. Sixty eight genes were re-expressed after 5-aza-2'-Deoxycitidine treatment and over-expressed in normal colorectal mucosa, including genes that were known to be methylated in CRC. After applying study selection criteria, we identified 16 potential genes. Two candidates were selected (ASPP1 and SCARA5). Among 15 CRC cell lines, methylation was identified in SCARA5 (20%). The methylation status of SCARA5 was subsequently investigated in 23 paired colorectal tissue samples; methylation was detected in 17%, respectively. Observed promoter methylation showed a tendency towards methylation in tumor-derived samples, in SCARA5 gene. Significant down expression of SCARA5 mRNA was observed in CRC cell lines and tumor tissues compared to adjacent normal tissues (P < 0.001 and P = 0.001, respectively). The use of genome-wide screening led to the identification of a group of candidate genes. Among them, SCARA5 was methylated and markedly down-regulated in CRC. SCARA5 gene may have a role in CRC tumorigenesis.
2012-03-20 | GSE32323 | GEO
Project description:Astrocytomas are common and lethal human brain tumors. Here, we have analyzed the methylation status of over 28,000 CpG islands and 18,000 promoters in normal human brain and in astrocytomas of various grades using the methylated-CpG island recovery assay (MIRA). We identified six to seven thousand methylated CpG islands in normal human brain. ~5% of the promoter-associated CpG islands in normal brain are methylated. Promoter CpG island methylation is inversely and intragenic methylation is directly correlated with gene expression levels in brain tissue. In astrocytomas, several hundred CpG islands undergo specific hypermethylation relative to normal brain with 428 methylation peaks common to more than 25% of the tumors. Genes involved in brain development and neuronal differentiation, such as POU4F3, GDNF, OTX2, NEFM, CNTN4, OTP, SIM1, FYN, EN1, CHAT, GSX2, NKX6-1, RAX, PAX6, DLX2, were strongly enriched among genes frequently methylated in tumors. There was an overrepresentation of homeobox genes and 31% of the most commonly methylated genes represent targets of the Polycomb complex. We identified several chromosomal loci in which many (sometimes more than 20) consecutive CpG islands were hypermethylated in tumors. Seven of such loci were near homeobox genes, including the HOXC and HOXD clusters, and the BARHL2, DLX1, and PITX2 genes. Two other clusters of hypermethylated islands were at sequences of recent gene duplication events. Our analysis offers mechanistic insights into brain neoplasia suggesting that methylation of genes involved in neuronal differentiation, perhaps in cooperation with other oncogenic events, may shift the balance from regulated differentiation towards gliomagenesis. Comparison of methylation patterns of 30 astrocytomas and 6 controls
2010-05-16 | E-GEOD-19391 | biostudies-arrayexpress