Epigenome analysis to identify DNA methylation changes associated with colorectal carcinogenesis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37872 | GEO | 2019/03/22
REPOSITORIES: GEO
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Project description:Colorectal cancer (CRC) is a genetically heterogeneous disease with several distinct morphological growth patterns. This study was aimed to investigate genes differentially expressed between ulcerative and polypoid colorectal CRC. cDNA microarray was first employed to compare the gene expression profiling of ulcerative and polypoid CRC with paired normal mucosa. Potential candidates identified by data filtering were further validated using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry. Epigenetic regulation of gene expression was investigated using methylation-specific PCR (MSP). cDNA microarray identified 11 up-regulated and 14 down-regulated genes differentially expressed in both types of tumor compared to matched normal mucosa. Among them, S100P was the only upregulated gene preferentially associated with polypoid CRC (p = 0.032), whereas no genes demonstrated significantly differential association with ulcerative CRC. S100P protein and mRNA expression level of polypoid CRC was significantly higher than that of ulcerative CRC (p < 0.05, respectively). Immunoreactivity of S100P protein was localized predominantly in the nuclei and to a less extent in the cytoplasm. Overexpression of S100P occurred early in the adenoma stage. 80% (24/30) and 20% (6/30) polypoid CRC showed diffusely strong and moderate overexpression, respectively. In contrast, S100P was diffusely and strongly expressed in 15% (6/40) ulcerative CRC, with 52.5% (21/40) and 32.5% (13/40) tumors having moderate and weak overexpression, respectively. S100P overexpression was preferentially associated with polypoid CRC (p < 0.001). The relative methylation level determined by MSP was not statistically different between polypoid and ulcerative CRC (43.36% vs. 49.10%, p = 0.168), indicating that promoter hypomethylation was directly related to upregulation of S100P mRNA. The gene expression profiling of ulcerative and polypoid CRC with paired normal mucosa were compared. Dye swapping experiments with ulcerative CRC vs normal mucosa or polypoid CRC vs normal mucosa were performed and we averaged the log ratios of the duplicated spots on each slide.
2013-05-16 | E-GEOD-46905 | biostudies-arrayexpress
Project description:Colorectal cancer (CRC) is a genetically heterogeneous disease with several distinct morphological growth patterns. This study was aimed to investigate genes differentially expressed between ulcerative and polypoid colorectal CRC. cDNA microarray was first employed to compare the gene expression profiling of ulcerative and polypoid CRC with paired normal mucosa. Potential candidates identified by data filtering were further validated using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry. Epigenetic regulation of gene expression was investigated using methylation-specific PCR (MSP). cDNA microarray identified 11 up-regulated and 14 down-regulated genes differentially expressed in both types of tumor compared to matched normal mucosa. Among them, S100P was the only upregulated gene preferentially associated with polypoid CRC (p = 0.032), whereas no genes demonstrated significantly differential association with ulcerative CRC. S100P protein and mRNA expression level of polypoid CRC was significantly higher than that of ulcerative CRC (p < 0.05, respectively). Immunoreactivity of S100P protein was localized predominantly in the nuclei and to a less extent in the cytoplasm. Overexpression of S100P occurred early in the adenoma stage. 80% (24/30) and 20% (6/30) polypoid CRC showed diffusely strong and moderate overexpression, respectively. In contrast, S100P was diffusely and strongly expressed in 15% (6/40) ulcerative CRC, with 52.5% (21/40) and 32.5% (13/40) tumors having moderate and weak overexpression, respectively. S100P overexpression was preferentially associated with polypoid CRC (p < 0.001). The relative methylation level determined by MSP was not statistically different between polypoid and ulcerative CRC (43.36% vs. 49.10%, p = 0.168), indicating that promoter hypomethylation was directly related to upregulation of S100P mRNA.
2013-05-16 | GSE46905 | GEO
Project description:Dysregulated miRNA in human colorectal cancer (CRC) were identified through comparison between 4 CRC tumors and their adjacent normal tissues by miRNA array. Histologically-confirmed CRC were included in this study. CRC tissues and paired adjacent normal tissues were obtained from the resected surgical specimens. The adjacent normal tissue is composed of normal colonic mucosa located at approximately 10 cm away from the cancer tissue. miRNA profiling of 754 human miRNAs was performed using TaqMan Human MiRNA Array Set v3.0. Quantitative real-time polymerase chain reaction (Q-PCR) was performed using Applied Biosystems 7900HT Real-Time PCR System (Applied Biosystems). Results were analyzed by the SDS RQ Manager 1.2 software (Applied Biosystems). 4 CRC tissues and 4 adjacent normal tissues were subjucted to qPCR based miRNA expression profiling. Equal amount of total RNA were used for analysis.
2013-03-20 | E-GEOD-45349 | 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. 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:Dysregulated miRNA in human colorectal cancer (CRC) were identified through comparison between 4 CRC tumors and their adjacent normal tissues by miRNA array. Histologically-confirmed CRC were included in this study. CRC tissues and paired adjacent normal tissues were obtained from the resected surgical specimens. The adjacent normal tissue is composed of normal colonic mucosa located at approximately 10 cm away from the cancer tissue. miRNA profiling of 754 human miRNAs was performed using TaqMan Human MiRNA Array Set v3.0. Quantitative real-time polymerase chain reaction (Q-PCR) was performed using Applied Biosystems 7900HT Real-Time PCR System (Applied Biosystems). Results were analyzed by the SDS RQ Manager 1.2 software (Applied Biosystems).
2013-03-20 | GSE45349 | GEO
Project description:To determine the pattern of copy number alterations that characterizes Crohn’s disease associated colorectal carcinomas (CD-CRCs), we performed array-based comparative genomic hybridization (aCGH) of CD-CRCs. As control group, we used histomorphologically similar sporadic mucinous colorectal adenocarcinomas. To gain insight into the dynamics of copy number alterations in CD associated colorectal tumor development, we additionally analyzed non-dysplastic, i.e., normal or inflamed, mucosa samples and dysplastic lesions from CD-CRC patients by aCGH. This revealed the gain of chromosome arm 5p as a distinctive feature of CD related colorectal carcinogenesis, while the overall pattern of copy number changes in CD-CRC was similar to sporadic mucinous CRC, including gains of chromosomes and chromosome arms 7, 8, 13 and 20q, and losses of 5q, 8p, 17p and 18q.
2018-06-30 | GSE113015 | GEO
Project description:Colorectal cancer (CRC) is the third most common cancer worldwide. Colorectal polyps are recognised pre-cursors of CRC, however hyperplastic polyps lack malignant potential. The purpose of this study was to identify differences in gene expression between normal colonic mucosa, hyperplastic and adenomatous polyps from disease-free individuals. By comparing polyps believed to have malignant potential (adenomatous polyps) with hyperplastic polyps it is hoped that new insights into colorectal carcinogenesis can be achieved. 24 colonic samples comprising 8 normal colonic mucosa, 8 hyperplastic polyps and 8 adenomatous polyps.
2012-08-25 | E-GEOD-40362 | biostudies-arrayexpress
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2018-09-22 | GSE120300 | GEO
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