Genome-wide DNA methylation profiling reveals a novel hypermethylated biomarker PRKCB in gastric cancer
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ABSTRACT:
PROVIDER: PRJNA1135692 | ENA |
REPOSITORIES: ENA
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Project description:Gastric cancer (GC) is one of the most common malignancies worldwide. Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Here, we profile the DNA methylation pattern of GC and identify promising diagnostic epigenetic biomarkers.
2024-11-13 | GSE272207 | GEO
Project description:Globally, gastric cancer (GC) ranks among the most prevalent forms of malignancy, posing a significant health burden. Epigenetic modifications, predominantly characterized by alterations in DNA methylation patterns, have been linked to a diverse array of neoplastic processes. Here, we undertake a comprehensive analysis of the DNA methylation signature in GC, with the aim to discover the potential diagnostic epigenetic biomarkers. Utilizing the Illumina 935 K BeadChip, we conducted a genome-wide exploration of DNA methylation patterns in four paired samples of GC tissues and adjacent non-cancerous counterparts. The bisulfite-pyrosequencing (n = 7) was employed to the quantification for methylated gene. The pubic databases including GWAS Catalog, TCGA and GEO were used. The immunohistochemistry and qRT-PCR analysis were performed. In contrast to adjacent tissues, GC tissues manifested pronounced hypermethylation patterns specifically within the promoter cytosine-phosphate-guanine (CpG) islands, indicating localized epigenetic alterations. DNA methylome analysis further revealed 4432 differentially-methylated probes (DMPs), with the gene PRKCB exhibited the most prominent average DNA methylation disparity (mean Δβ = 0.353). Pyrosequencing validation confirmed three DMPs within the PRKCB promoter (cg08406370, cg00735962, and cg18526361). Notably, the mean methylation levels of PRKCB were inversely correlated with mRNA expression levels in the GWAS Catalog. Furthermore, both mRNA and protein expression levels of PRKCB were significantly reduced in GCs when compared to their adjacent non-cancerous counterparts, verified by TCGA and GEO database. Our study reveals significant DNA methylation alterations in GC and emphasizes the pivotal role of PRKCB gene hypermethylation in conferring GC risk, which offers fresh perspectives for advancing diagnostic approaches and therapeutic strategies for GC.
| S-EPMC11535215 | biostudies-literature
Project description:A novel urinary microRNA biomarker panel for detecting gastric cancer
| PRJNA528633 | ENA
Project description:BackgroundEpigenetic alternation is a common contributing factor to neoplastic transformation. Although previous studies have reported a cluster of aberrant promoter methylation changes associated with silencing of tumor suppressor genes, little is known concerning their sequential DNA methylation changes during the carcinogenetic process. The aim of the present study was to address a genome-wide search for identifying potentially important methylated changes and investigate the onset and pattern of methylation changes during the progression of colorectal neoplasia.MethodsA three-phase design was employed in this study. In the screening phase, DNA methylation profile of 12 pairs of colorectal cancer (CRC) and adjacent normal tissues was analyzed by using the Illumina MethylationEPIC BeadChip. Significant CpG sites were selected based on a cross-validation analysis from The Cancer Genome Atlas (TCGA) database. Methylation levels of candidate CpGs were assessed using pyrosequencing in the training dataset (tumor lesions and adjacent normal tissues from 46 CRCs) and the validation dataset (tumor lesions and paired normal tissues from 13 hyperplastic polyps, 129 adenomas, and 256 CRCs). A linear mixed-effects model was used to examine the incremental changes of DNA methylation during the progression of colorectal neoplasia.ResultsThe comparisons between normal and tumor samples in the screening phase revealed an extensive CRC-specific methylomic pattern with 174,006 (21%) methylated CpG sites, of which 22,232 (13%) were hyermethylated and 151,774 (87%) were hypomethylated. Hypermethylation mostly occurred in CpG islands with an overlap of gene promoters, while hypomethylation tended to be mapped far away from functional regions. Further cross validation analysis from TCGA dataset confirmed 265 hypermethylated promoters coupling with downregulated gene expression. Among which, hypermethylated changes in MEEPD2 promoter was successfully replicated in both training and validation phase. Significant hypermethylation appeared since precursor lesions with an extensive modification in CRCs. The linear mixed-effects modeling analysis found that a cumulative pattern of MPPED2 methylation changes from normal mucosa to hyperplastic polyp to adenoma, and to carcinoma (P < 0.001).ConclusionsOur findings indicate that epigenetic alterations of MPPED2 promoter region appear sequentially during the colorectal neoplastic progression. It might be able to serve as a promising biomarker for early diagnosis and stage surveillance of colorectal tumorigenesis.
| S-EPMC6407227 | biostudies-literature
Project description:Purpose: Gastric cancer (GC) is one of the most common causes of cancer deaths worldwide; however, reliable and non-invasive screening methods for GC are not established. Therefore, we conducted this study to develop a biomarker for GC detection, consisting of urinary microRNAs (miRNAs). Experimental Design: We matched 306 participants by age and sex (153 pairs consisting of patients with GC and healthy controls [HCs]), then randomly divided them across three groups: (1) the discovery cohort (4 pairs); (2) the training cohort (95 pairs); (3) the validation cohort (54 pairs). Moreover, 64 participants (32 pairs) with serum samples were also enrolled in the serum cohort. Result: There were 22 urinary miRNAs with significantly aberrant expressions between the two groups in the discovery cohort. Upon multivariate analysis of the training cohort, urinary expression levels of miR-6807-5p and miR-6856-5p were significantly independent biomarkers for diagnosis of GC, in addition to Helicobacter pylori (H. pylori) status. A diagnostic panel that combined the aberrant miRNAs and H. pylori status distinguished between HC and GC samples with an area under the curve (AUC) = 0.736. In the validation cohort, urinary miR-6807-5p and miR-6856-5p showed significantly higher expression levels in the GC group, and the combination biomarker panel of miR-6807-5p, miR-6856-5p, and H. pylori status also showed excellent performance (AUC = 0.885). In addition, serum levels of miR-6807-5p and miR-6856-5p were significantly higher in the GC group. Conclusion: This novel biomarker panel enables early and non-invasive detection of GC.
2019-12-22 | GSE128720 | GEO
Project description:Gastric cancer is one of the most lethal malignancies with high mortality and gastric cancer-specific biomarker is need due to the lack of specific method for early screening, diagnosis, and prognosis of the patients with gastric cancer. Ascites is known for an important source for conducing biomarker discovery because it contains the secreted proteins from malignant cells, growth factors, and cytokines. In this study, we have conducted a comprehensive proteome study using ascites of patients with inflammatory diseases and gastric cancer. In the discovery stage, we have identified 2761 ascites-specific proteins, where 234 proteins were quantitated using the label free quantitation method, the normalized spectral abundance factor (NSAF); 152 and 82 proteins showed up and down-regulated pattern, respectively. Our ascites proteome can be used as baseline data for the discovery of novel biomarkers of the gastric cancer.
2018-04-16 | PXD002213 | Pride
Project description:DNA-hypermethylated human gastric cancer circumvents apoptosis in the absence of TP53 mutation (RNA-Seq)
| PRJNA994964 | ENA
Project description:Colorectal cancer (CRC) is one of the most common forms of cancer and the second leading cause of cancer-related deaths in the western world.
CRC mortality is related to stage of disease with a five year survival for early-stage disease of 77.0% and 50.8% for late stage disease. Methods for early detection of primary as well as recurrent CRC are therefore important to increase patient survival. Tumour biomarkers from blood, stool, or urine could aid the early diagnostics of CRC, but despite extensive research such markers have only provided limited clinical value.
Sporadic CRC develops as a result of the accumulation of genetic and epigenetic alterations. Epigenetic alterations include DNA hypermethylation, which through transcriptional silencing of tumour suppressor genes is associated with cancer development and cancer progression. The search for gene promoter regions hypermethylated in cancer has been ongoing for nearly two decades, and a number of genes have been shown to be preferentially hypermethylated in CRC. Therefore, hypermethylated DNA in plasma has been suggested as a marker for tumour-stage and survival in CRC patients. The only approved biomarker for the detection of CRC recurrence is the protein carcinoembryonic antigen (CEA). CEA is limited by its low sensitivity and therefore not recommended as a diagnostic biomarker. Hypermethylation of CRC specific genes as part of a molecular biomarker panel measured in blood could prove to be a recurrence marker in CRC patients, with elevated sensitivity and specificity.
The aims of this project are to examine if hypermethylation of specific genes measured from cell-free DNA in plasma of CRC patients can be used to detect primary CRC, to detect CRC recurrence and to be a biomarker for CRC prognosis.
Development of a reliable sensitive and specific biomarker for CRC will immensely improve the diagnostics and handling of CRC patients.
| 2227102 | ecrin-mdr-crc
Project description:Extracellular RNA (exRNA) is an emerging paradigm as endocrine signals in cellular communication, biomarker development, therapeutic applications and systemic physiology. This project is to test the hypothesis that salivary extracellular RNA (exRNA) can be developed for the clinical detection of human diseases. Our laboratory first reported the existence of a transcriptome and microRNA profile in cell free saliva followed by its scientific characterizations and clinical utilities including biomarker development for molecular oncology applications. Most recently we have performed RNA-sequencing in cell free saliva and reported three major types of RNA in saliva (mRNA, miRNA and snoRNA). This study is to test the hypothesis that salivary exRNA can be developed to detect gastric cancer by performing a biomarker development study to definitively validate salivary exRNA biomarkers for the detection of gastric cancer.
2018-10-27 | GSE121870 | GEO
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