Genome-Wide DNA Methylation Profiles of Low- and High-Grade Adenoma Reveals Potential Biomarkers for Early Diagnosis of Colorectal Carcinoma
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PROVIDER: PRJNA579557 | ENA |
REPOSITORIES: ENA
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Project description:Abnormal DNA methylation is a hallmark of human cancers and may be a promising biomarker for early diagnosis of human cancers1. However, the majority of DNA methylation biomarkers that have been identified are based on the hypothesis that early differential methylation regions (DMRs) are maintained throughout carcinogenesis and could be detected at all stages of cancer. In this study, we identified potential early biomarkers of colorectal cancer (CRC) development by genome-wide DNA methylation assay (Illumina infinium450, 450K) to normal (N=20) and pre-colorectal cancer samples including 18 low-grade adenoma (LGA) and 22 high-grade adenoma (HGA).
2020-04-23 | GSE139404 | GEO
Project description:Genome wide DNA methylation of colon low grade and high grade adenoma
| PRJNA1218792 | ENA
Project description:Introduction: The dynamics of colorectal epigenetics during early carcinogenesis remain undocumented. In this study, we explore the DNA methylation dynamics in colorectal cancer oncogenesis from non-tumor colon tissues to low-grade, high-grade adenoma and adenocarcinoma. Methods: The methylome of 13 low-grade and 19 high-grade colorectal adenomas was determined using the EPIC v1 Human Methylation Beadchip. These methylation profiles were complemented with the methylomes of 206 non-tumor colon and 24 colon adenocarcinomas from GSE149282, GSE132804 series and the HCMI study. Differentially methylated CpG were identified by Student's t-test and used to monitor the evolution of the colon methylome during carcinogenesis. The differentially methylated promoters were used to infer the associated biological process using gene ontology. Results: 4.9% of the colon methylome is significantly altered (p < 10-4) during carcinogenesis with two thirds corresponding to DNA demethylation. 56.6% of the methylation changes occurs at the transition from non-tumor colon tissues to low-grades adenomas. 18.2% of the DNA methylation changes are transitory during low-grade and/or high-grade adenomas. The biological pathways sensory perception of odor and stimulus were early unmethylated, nervous system development and homophilic cell adhesion were early methylated, and chemical synaptic transmission and cell adhesion were transiently methylated. Conclusion: This study provides insight into the dynamics of colonic epigenetics during carcinogenesis, with early DNA methylation changes in the low-grade adenomas associated with transient DNA methylation changes. However, the causality of these changes remains to be elucidated.
2025-12-18 | GSE288652 | GEO
Project description:Most of the carcinogenesis of colorectal cancer (CRC) follows the normal-adenoma-carcinoma (N-A-C) sequence. We aimed to identify the key proteins in the N-A-C sequence and describe the proteomic pattern of tubular adenoma, tubulovillous adenoma and high-grade neoplasia. This study used high-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with quantitative 5-plex tandem mass tag labeling, to profile protein changes in normal epithelium, tubular adenoma, tubulovillous adenoma, high-grade neoplasia, cancer tissues in colorectum.
2021-01-30 | PXD023899 |
Project description:Primary outcome(s): The diagnostic accuracy of low grade adenoma using EC normal pit (NP) sign in endoscopic images
| 2653008 | ecrin-mdr-crc
Project description:Epigenetic modifications, such as aberrant DNA promoter methylation is frequently observed in cervical cancer. Identification of hypermethylated regions maybe useful for discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3) or worse may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions were characterised using genome-wide methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methyl-DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium resulting in the identification of hypermethylated differentially methylated regions (DMRs). Validation of 9 selected DMRs by MSP or BSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was applied exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples (p<0.001). Clinical validation of both markers in cervical scrapings from patients referred with an abnormal cervical smear, confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion (p<0.001) and the ROC analysis was discriminative (p<0.005). These possible methylation markers represent COL25A1 and KATNAL2 promoters and their observed increased methylation upon progression is in agreement with their biological function (cytoskeleton regulation). In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and could be potential biomarkers for early detection. Epigenetic modifications, such as aberrant DNA promoter methylation is frequently observed in cervical cancer. Identification of hypermethylated regions maybe useful for discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3) or worse may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions were characterised using genome-wide methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methyl-DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium resulting in the identification of hypermethylated differentially methylated regions (DMRs). Validation of 9 selected DMRs by MSP or BSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was applied exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples (p<0.001). Clinical validation of both markers in cervical scrapings from patients referred with an abnormal cervical smear, confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion (p<0.001) and the ROC analysis was discriminative (p<0.005). These possible methylation markers represent COL25A1 and KATNAL2 promoters and their observed increased methylation upon progression is in agreement with their biological function (cytoskeleton regulation). In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and could be potential biomarkers for early detection. MeDIP with subsequent microarray analysis was performed on DNA isolated from frozen macrodissected epithelial tissue of CIN3 lesions (n=15) and normal cervices (n=10).
2012-11-01 | E-GEOD-36319 | biostudies-arrayexpress
Project description:Identification of differentially expressed microRNAs as potential biomarkers for carcinoma ex pleomorphic adenoma
| PRJNA847079 | ENA
Project description:Objective: Ovarian tumors of low-malignant potential (LMP) and low-grade serous ovarian carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from that of high-grade serous ovarian carcinoma. Past studies have utilized gene expression profiles to support this theory. The objective of the current study was to identify new genes whose expression profiles in LMP ovarian tumors and low-grade ovarian carcinomas differ from that in high-grade ovarian carcinomas. Methods: We used RNA from 3 normal human ovarian surface epithelia (HOSE) and from 10 low-grade and 10 high-grade serous ovarian carcinoma samples to perform gene expression profiling. Using real-time reverse-transcription polymerase chain reaction (RT-PCR), we evaluated changes in PAX2 mRNA expression in cDNA created from RNA extracted from an independent set of ovarian tissue samples (7 LMP tumors and 17 low-grade and 23 high-grade serous carcinomas). We also examined PAX2 expression using Western blot analysis of protein extracted from a set of ovarian LMP and low- and high-grade carcinoma tissue samples. Additionally, we used immunohistochemistry (IHC) to validate PAX2 overexpression in a third independent set of paraffin ovarian tissue sections from 17 LMP tumors and 16 low- and 257 high-grade carcinomas. Results: Gene profiling revealed higher expression of PAX2 in low-grade than in high-grade ovarian carcinomas. Real-time RT-PCR demonstrated a statistically significant difference in median PAX2 mRNA expression, expressed as fold change, among ovarian LMP tumor (1837.38), low-grade (183.12), and high-grade (3.72) carcinoma samples (p=0.015). Western blot analysis revealed strong PAX2 expression in ovarian LMP and low-grade carcinoma samples but no PAX2 protein expression in high-grade carcinomas. On IHC, more LMP tumor and low-grade carcinoma samples expressed moderate to high levels of PAX2 than did high-grade ovarian carcinoma samples. The numbers of samples with strong nuclear staining was significantly higher for ovarian LMP tumors (10 of 17, p<0.001) and low-grade serous carcinomas (10 of 16, p<0.001) than for high-grade carcinomas (27 of 257). Discussion: Our identification and validation of higher PAX2 expression in ovarian LMP tumors and low-grade serous carcinomas than in high-grade carcinomas supports the two-tiered hypothesis that the first two are on a continuum and are distinct from high-grade ovarian carcinomas. PAX2 may represent a potential biomarker and future therapeutic target for individualizing chemotherapy for ovarian LMP tumors and low-grade carcinomas in the future.
2009-05-31 | GSE14001 | GEO
Project description:Acute pulmonary embolism (APE) remains among the most formidable challenges facing public health practice in the 21st century. Accurate diagnosis of APE is severely hindered by the lack of biomarkers with both high sensitivity and specificity. MicroRNAs (miRNAs) involve various pathophysiologic processes underlying multitudinous diseases. Accmulating evidences point to the fact that miRNAs may serve as ideal biomarkers.The aim of the present study was to explore the potential of plasma miRNAs as biomarkers for diagnosis of APE. Two TaqMan miRNA arrays were performed on plasma of 10 APE patients and 10 healthy controls.
2013-08-08 | E-GEOD-24149 | biostudies-arrayexpress
Project description:Differentially expressed noncoding RNAs as potential biomarkers for DIPG diagnosis and prognosis
| PRJNA575738 | ENA