scholarly journals Integrative Analysis of Epigenome and Transcriptome Data Reveals Aberrantly Methylated Promoters and Enhancers in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Peng Huang ◽  
Mengxiang Xu ◽  
Haijun Han ◽  
Xinyi Zhao ◽  
Ming D. Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Dna Methylation ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Differentially Methylated Region ◽  
Transcriptome Data ◽  
Rna Seq ◽  
Genome Bisulfite Sequencing ◽  
Aberrant Dna Methylation

DNA methylation is a key transcription regulator, whose aberration was ubiquitous and important in most cancers including hepatocellular carcinoma (HCC). Whole-genome bisulfite sequencing (WGBS) was conducted for comparison of DNA methylation in tumor and adjacent tissues from 33 HCC patients, accompanying RNA-seq to determine differentially methylated region-associated, differentially expressed genes (DMR-DEGs), which were independently replicated in the TCGA-LIHC cohort and experimentally validated via 5-aza-2-deoxycytidine (5-azadC) demethylation. A total of 9,867,700 CpG sites showed significantly differential methylation in HCC. Integrations of mRNA-seq, histone ChIP-seq, and WGBS data identified 611 high-confidence DMR-DEGs. Enrichment analysis demonstrated activation of multiple molecular pathways related to cell cycle and DNA repair, accompanying repression of several critical metabolism pathways such as tyrosine and monocarboxylic acid metabolism. In TCGA-LIHC, we replicated about 53% of identified DMR-DEGs and highlighted the prognostic significance of combinations of methylation and expression of nine DMR-DEGs, which were more efficient prognostic biomarkers than considering either type of data alone. Finally, we validated 22/23 (95.7%) DMR-DEGs in 5-azadC-treated LO2 and/or HepG2 cells. In conclusion, integration of epigenome and transcriptome data depicted activation of multiple pivotal cell cycle-related pathways and repression of several metabolic pathways triggered by aberrant DNA methylation of promoters and enhancers in HCC.

scholarly journals Aberrant DNA methylation of imprinted loci in hepatocellular carcinoma and after in vitro exposure to common risk factors

2015 ◽  
Vol 7 (1) ◽  
pp. 15 ◽  
Author(s):  
Marie-Pierre Lambert ◽  
Pierre-Benoit Ancey ◽  
Davide Esposti ◽  
Marie-Pierre Cros ◽  
Athena Sklias ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
In Vitro Exposure ◽  
Common Risk Factors ◽  
Aberrant Dna Methylation

scholarly journals Identification of a five-gene signature in association with overall survival for hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11273
Author(s):  
Lei Yang ◽  
Weilong Yin ◽  
Xuechen Liu ◽  
Fangcun Li ◽  
Li Ma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Overall Survival ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Enrichment Score ◽  
Hub Genes ◽  
Cox Regression Analysis

Background Hepatocellular carcinoma (HCC) is considered to be a malignant tumor with a high incidence and a high mortality. Accurate prognostic models are urgently needed. The present study was aimed at screening the critical genes for prognosis of HCC. Methods The GSE25097, GSE14520, GSE36376 and GSE76427 datasets were obtained from Gene Expression Omnibus (GEO). We used GEO2R to screen differentially expressed genes (DEGs). A protein-protein interaction network of the DEGs was constructed by Cytoscape in order to find hub genes by module analysis. The Metascape was performed to discover biological functions and pathway enrichment of DEGs. MCODE components were calculated to construct a module complex of DEGs. Then, gene set enrichment analysis (GSEA) was used for gene enrichment analysis. ONCOMINE was employed to assess the mRNA expression levels of key genes in HCC, and the survival analysis was conducted using the array from The Cancer Genome Atlas (TCGA) of HCC. Then, the LASSO Cox regression model was performed to establish and identify the prognostic gene signature. We validated the prognostic value of the gene signature in the TCGA cohort. Results We screened out 10 hub genes which were all up-regulated in HCC tissue. They mainly enrich in mitotic cell cycle process. The GSEA results showed that these data sets had good enrichment score and significance in the cell cycle pathway. Each candidate gene may be an indicator of prognostic factors in the development of HCC. However, hub genes expression was weekly associated with overall survival in HCC patients. LASSO Cox regression analysis validated a five-gene signature (including CDC20, CCNB2, NCAPG, ASPM and NUSAP1). These results suggest that five-gene signature model may provide clues for clinical prognostic biomarker of HCC.

scholarly journals Identification and prognostic value of DLGAP5 in endometrial cancer

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10433
Author(s):  
Ruoyi Zheng ◽  
Zhengzheng Shi ◽  
Wenzhi Li ◽  
Jianqin Yu ◽  
Yuli Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Endometrial Cancer ◽  
Survival Data ◽  
Cell Cycle Regulation ◽  
Prognostic Significance ◽  
Venn Diagram ◽  
Clinical Samples ◽  
Transcriptome Data ◽  
Normal Tissues ◽  
Cycle Regulation

Background Endometrial cancer poses a serious threat to women’s health worldwide, and its pathogenesis, although actively explored, is not fully understood. DLGAP5 is a recently identified cell cycle-regulation gene not reported in endometrial cancer. This study was aiming to analyze the role of DLGAP5 in tumorigenesis and development and to investigate its prognostic significance of patients with endometrial cancer. Methodology Microarray datasets (GSE17025, GSE39099 and GSE63678) from the GEO database were used for comparative analysis, and their intersection was obtained by applying the Venn diagram, and DLGAP5 was selected as the target gene. Next, transcriptome data (n = 578) was downloaded from TCGA-UCEC to analyze the mRNA expression profile of DLGAP5. Then, immunohistochemical data provided by HPA were used to identify the different protein expression levels of DLGAP5 in tumor tissues and normal tissues. Subsequently, the prognostic meaning of DLGAP5 in patients with endometrial cancer was explored based on survival data from TCGA-UCEC (n = 541). Finally, the reliability of DLGAP5 expression was verified by RT-qPCR. Results Transcriptome data from TCGA-UCEC, immunohistochemical data from HPA, and RT-qPCR results from clinical samples were used for triple validation to confirm that the expression of DLGAP5 in endometrial cancer tissues was significantly higher than that in normal endometrial tissues. Kaplan–Meier survival analysis announced that the expression level of DLGAP5 was negatively correlated with the overall survival of patients with endometrial cancer. Conclusions DLGAP5 is a potential oncogene with cell cycle regulation, and its overexpression can predict the poor prognosis of patients with endometrial cancer. As a candidate target for the diagnosis and treatment of endometrial cancer, it is worthwhile to make further study to reveal the carcinogenicity of DLGAP5 and the mechanism of its resistance of organisms.

Abstract 5040: Aberrant DNA methylation of microRNAs in hepatocellular carcinoma

2012 ◽  
Author(s):  
Jing Shen ◽  
Shuang Wang ◽  
Yu-Jing Zhang ◽  
Maya Kappil ◽  
Hui-Chen Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Aberrant Dna Methylation

Aberrant DNA methylation profile and frequent methylation ofKLK10andOXGR1genes in hepatocellular carcinoma

2009 ◽  
Vol 48 (12) ◽  
pp. 1057-1068 ◽  
Author(s):  
Chang-Yi Lu ◽  
Sen-Yung Hsieh ◽  
Yen-Jung Lu ◽  
Chi-Sheng Wu ◽  
Lih-Chyang Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Methylation Profile ◽  
Dna Methylation Profile ◽  
Aberrant Dna Methylation

scholarly journals Elucidating the Landscape of Aberrant DNA Methylation in Hepatocellular Carcinoma

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e55761 ◽  
Author(s):  
Min-Ae Song ◽  
Maarit Tiirikainen ◽  
Sandi Kwee ◽  
Gordon Okimoto ◽  
Herbert Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Aberrant Dna Methylation

scholarly journals DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1530
Author(s):  
Marisa Flook ◽  
Alba Escalera-Balsera ◽  
Alvaro Gallego-Martinez ◽  
Juan Manuel Espinosa-Sanchez ◽  
Ismael Aran ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Hearing Loss ◽  
Mononuclear Cells ◽  
Cpg Island ◽  
Enrichment Analysis ◽  
Meniere Disease ◽  
Disease Mechanisms ◽  
Significant Heritability ◽  
Genome Bisulfite Sequencing ◽  
Menière Disease

Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed on MD. Here we performed whole-genome bisulfite sequencing in 14 MD patients and six healthy controls, with the aim of identifying an MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (n= 9545), several of them in hearing loss genes, such as PCDH15, ADGRV1 and CDH23. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including two UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows distinguishing between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.

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