scholarly journals Discovery of Molecular DNA Methylation-Based Biomarkers through Genome-Wide Analysis of Response Patterns to BCG for Bladder Cancer

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1839
Author(s):  
Dafina Ilijazi ◽  
Walter Pulverer ◽  
Iris E. Ertl ◽  
Ursula Lemberger ◽  
Shoji Kimura ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Focal Adhesion ◽  
Intravesical Therapy ◽  
Bacterial Invasion ◽  
Genome Wide Analysis ◽  
Bcg Immunotherapy ◽  
Genome Wide ◽  
A Genome ◽  
Bcg Therapy ◽  
Significant Difference

Background: Bacillus Calmette-Guérin (BCG) immunotherapy, the standard adjuvant intravesical therapy for some intermediate and most high-risk non-muscle invasive bladder cancers (NMIBCs), suffers from a heterogenous response rate. Molecular markers to help guide responses are scarce and currently not used in the clinical setting. Methods: To identify novel biomarkers and pathways involved in response to BCG immunotherapy, we performed a genome-wide DNA methylation analysis of NMIBCs before BCG therapy. Genome-wide DNA methylation profiles of DNA isolated from tumors of 26 BCG responders and 27 failures were obtained using the Infinium MethylationEPIC BeadChip. Results: Distinct DNA methylation patterns were found by genome-wide analysis in the two groups. Differentially methylated CpG sites were predominantly located in gene promoters and gene bodies associated with bacterial invasion of epithelial cells, chemokine signaling, endocytosis, and focal adhesion. In total, 40 genomic regions with a significant difference in methylation between responders and failures were detected. The differential methylation state of six of these regions, localized in the promoters of the genes GPR158, KLF8, C12orf42, WDR44, FLT1, and CHST11, were internally validated by bisulfite-sequencing. GPR158 promoter hypermethylation was the best predictor of BCG failure with an AUC of 0.809 (p-value < 0.001). Conclusions: Tumors from BCG responders and BCG failures harbor distinct DNA methylation profiles. Differentially methylated DNA regions were detected in genes related to pathways involved in bacterial invasion of cells or focal adhesion. We identified candidate DNA methylation biomarkers that may help to predict patient prognosis after external validation in larger, well-designed cohorts.

scholarly journals A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in the LPA promoter

PLoS ONE ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. e0232073
Author(s):  
Stefan Coassin ◽  
Natascha Hermann-Kleiter ◽  
Margot Haun ◽  
Simone Wahl ◽  
Rory Wilson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Novel Association

scholarly journals DNA methylation and body-mass index: a genome-wide analysis

The Lancet ◽  
2014 ◽  
Vol 383 (9933) ◽  
pp. 1990-1998 ◽  
Author(s):  
Katherine J Dick ◽  
Christopher P Nelson ◽  
Loukia Tsaprouni ◽  
Johanna K Sandling ◽  
Dylan Aïssi ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome

scholarly journals Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation

2014 ◽  
Vol 33 (5) ◽  
pp. 1355-1363 ◽  
Author(s):  
YOSHIJI YAMADA ◽  
TAMOTSU NISHIDA ◽  
HIDEKI HORIBE ◽  
MITSUTOSHI OGURI ◽  
KIMIHIKO KATO ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Hypermethylated Genes

scholarly journals Epigenetics biomarkers of delirium: immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients

2019 ◽  
Author(s):  
Taku Saito ◽  
Hiroyuki Toda ◽  
Gabrielle N. Duncan ◽  
Sydney S. Jellison ◽  
Tong Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Network Analysis ◽  
Tnf Alpha ◽  
Epigenetic Biomarkers ◽  
Genome Wide ◽  
A Genome ◽  
Significant Difference ◽  
Dnam Level

ABSTRACTBackgroundThe authors previously hypothesized the role of epigenetics in pathophysiology of delirium, and tested DNA methylation (DNAm) change among pro-inflammatory cytokines along with aging in blood, glia and neuron. The authors reported that DNAm level of the TNF-alpha decreases along with aging in blood and glia, but not in neuron; however, DNAm differences between delirium cases and non-delirium controls have not been investigated directly. Therefore, in the present study, DNAm differences in blood between delirium patients and controls without delirium were examined.MethodsA case-control study with 92 subjects was conducted. Whole blood samples were collected and genome-wide DNAm was measured by the Infinium HumanMethylationEPIC BeadChip arrays. The correlation between DNAm levels in the TNF-alpha and age, network analysis, and the correlation between age and DNAm age were tested.ResultsOnly delirium cases showed 3 CpGs sites in the TNF-alpha significantly correlated to age after multiple corrections. A genome-wide significant CpG site near the gene of LDLRAD4 was identified. In addition, network analysis showed several significant pathways with false discovery rate adjusted p-value < 0.05. The top pathway with GO was immune response, and the second top pathway with KEGG was cholinergic synapse. Although there was no statistically significant difference, DNAm age among non-delirium controls showed “slower aging” compared to delirium cases.ConclusionsDNAm differences were shown both at gene and network levels between delirium cases and non-delirium controls. This finding indicates that DNAm status in blood has a potential to be used as epigenetic biomarkers for delirium.

scholarly journals Epigenetic Variation in Monozygotic Twins: A Genome-Wide Analysis of DNA Methylation in Buccal Cells

Genes ◽  
2014 ◽  
Vol 5 (2) ◽  
pp. 347-365 ◽  
Author(s):  
Jenny van Dongen ◽  
Erik Ehli ◽  
Roderick Slieker ◽  
Meike Bartels ◽  
Zachary Weber ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Monozygotic Twins ◽  
Epigenetic Variation ◽  
Buccal Cells ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome

scholarly journals DNA methylation study of fetus genome through a genome-wide analysis

2014 ◽  
Vol 7 (1) ◽  
Author(s):  
Hong-Dan Wang ◽  
Qiao-Fang Hou ◽  
Qian-Nan Guo ◽  
Tao Li ◽  
Dong Wu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome

Reduction of T-Box 15 gene expression in tumor tissue as a prognostic biomarker for patients with hepatocellular carcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 341-341
Author(s):  
Yuji Morine ◽  
Tohru Utsunomiya ◽  
Satoru Imura ◽  
Tetsuya Ikemoto ◽  
Shuichi Iwahashi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Tumor Progression ◽  
Tumor Tissue ◽  
Mrna Levels ◽  
T Box ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Tumor Tissues ◽  
A Genome

341 Background: Genome-wide analysis is widely applied to detect molecular alterations in tumor and non-tumor tissue during oncogenesis and tumor progression. We analyzed DNA methylation profiles of hepatocellular carcinoma (HCC), which was is the third-highest cause of cancer-related deaths worldwide, and investigated the clinical role of most heyper-methylated gene, encodes T-box 15 (TBX15), which was originally involved in mesodermal differentiation. Methods: We used an Illumina Infinium HumanMethylation450 BeadChip Kit to conduct a genome-wide analysis of DNA methylation of tumor and non-tumor tissue of 15 patients with HCC. Methylation scores for CpG sites were assigned a Beta-value. Another validation set, which comprised 58 patients with HCC who underwent radical resection, was analyzed to investigate the relationships between tumor phenotype, prognosis, and TBX15 mRNA expression. Results: TBX15 was the most hyper-methylated gene (Beta-value in tumor tissue = 0.52 compared with non-tumor tissue), and TBX15 mRNA levels in tumor tissues were significantly lower compared with those of non-tumor tissues (p < 0.0001). When we assigned a cutoff value = 0.5-fold to define differential expression of TBX15 mRNA, low TBX15 expression significantly correlated with higher serum DCP levels, and the overall survival 5-year survival rates of the low-expression group (n = 17) were significantly shorter compared with those of the high-expression group (n = 41) (43.3% vs. 86.2%, p = 0.001). Multivariate analysis identified low TBX15 expression as an independent prognostic factor for overall and disease-free survival. Conclusions: Genome-wide DNA methylation profiling indicates that hypermethylation and reduced expression of TBX15 in tumor tissue represents a potential biomarker for predicting tumor progression and poor survival of patients with HCC.

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