The effect of key DNA methylation in different regions on gene expression in hepatocellular carcinoma

2021 ◽  
Author(s):  
Yu-Xian Liu ◽  
Qian-Zhong Li ◽  
Yan-Ni Cao
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Prognostic Factors ◽  
Potential Biomarkers

Four genes related to DNA methylation were found to be independent prognostic factors and potential biomarkers for hepatocellular carcinoma.

Integrative analysis of DNA methylation and gene expression identify a six epigenetic driver signature for predicting prognosis in hepatocellular carcinoma

2018 ◽  
Vol 234 (7) ◽  
pp. 11942-11950 ◽  
Author(s):  
Gan‐xun Li ◽  
Ze‐yang Ding ◽  
Yu‐wei Wang ◽  
Tong‐tong Liu ◽  
Wei‐xun Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Integrative Analysis

scholarly journals Trace Elements Status and Metallothioneins DNA Methylation Influence Human Hepatocellular Carcinoma Survival Rate

2021 ◽  
Vol 10 ◽  
Author(s):  
Silvia Udali ◽  
Domenica De Santis ◽  
Filippo Mazzi ◽  
Sara Moruzzi ◽  
Andrea Ruzzenente ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Trace Elements ◽  
Survival Rate ◽  
Inductively Coupled Plasma ◽  
Prognostic Significance ◽  
Promoter Dna Methylation ◽  
Promoter Dna

BackgroundMechanisms underlying hepatocellular carcinoma (HCC) development are largely unknown. The role of trace elements and proteins regulating metal ions homeostasis, i.e. metallothioneins (MTs), recently gained an increased interest. Object of the study was to investigate the role of promoter DNA methylation in MTs transcriptional regulation and the possible prognostic significance of serum trace elements in HCC.MethodsForty-nine HCC patients were enrolled and clinically characterized. Cu, Se, and Zn contents were measured by Inductively Coupled Plasma Mass Spectrometry in the serum and, for a subset of 27 patients, in HCC and homologous non-neoplastic liver (N) tissues. MT1G and MT1H gene expression in hepatic tissues was assessed by Real-Time RT-PCR and the specific promoter DNA methylation by Bisulfite-Amplicon Sequencing.ResultsPatients with Cu serum concentration above the 80th percentile had a significantly decreased survival rate (P < 0.001) with a marked increased hazard ratio for mortality (HR 6.88 with 95% CI 2.60–18.23, P < 0.001). Se and Zn levels were significantly lower in HCC as compared to N tissues (P < 0.0001). MT1G and MT1H gene expression was significantly down-regulated in HCC as compared to N tissues (P < 0.05). MTs promoter was hypermethylated in 9 out of the 19 HCC tissues showing MTs down-regulation and methylation levels of three specific CpGs paralleled to an increased mortality rate among the 23 patients analyzed (P = 0.015).ConclusionsMT1G and MT1H act as potential tumor suppressor genes regulated through promoter DNA methylation and, together with serum Cu concentrations, be related to survival rate in HCC.

scholarly journals Identification of factors regulating the gene expression of alcohol dehydrogenases in hepatocellular carcinoma

2021 ◽  
Author(s):  
Jinghe Xie ◽  
Yaqi Qiu ◽  
Shuai Zhang ◽  
Keqing Ma ◽  
Yimeng Ou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Copy Number ◽  
Gene Copy Number ◽  
Copy Number Variations ◽  
The Cancer Genome Atlas ◽  
Gene Copy ◽  
Excessive Alcohol Consumption ◽  
Alcohol Dehydrogenases

Abstract Background Excessive alcohol consumption has been documented to increase the risk of liver hepatocellular carcinoma (HCC) development. Accordingly, a broad interest pointed to alcohol dehydrogenases (ADHs), which display essential roles in alcohol metabolism. Despite the relevance of ADHs expression and the prognosis of HCC has been estimated, so far, limited research concerning the factors that are responsible for the regulation of ADHs expression has been reported. Methods In this study, using The Cancer Genome Atlas (TCGA) and RegNetwork database, we predicted potential factors consisting of DNA methylation, gene copy number variations, transcription factors (TFs) and microRNAs (miRNAs) that might impact ADHs gene expression in HCC. Results We found that DNA methylation induced the down-regulated expression of ADH1B. Of note, our results implicated that gene copy number variation might not have effects on ADHs expression. Regarding TFs, we speculated that NFYA modulated ADH1C, E2F1 and TFAP2A regulated ADH6 expression based on their expression and prognostic value. Moreover, miR-185 and miR-561 might elicit the repression of ADH4, and miR-105 might impair ADH6 expression. Conclusion This study revealed that multiple factors, including DNA methylation, TFs and microRNAs, affect the expression of ADH family members, which provided new insights into discovering promising HCC-suppressive targets.

scholarly journals Identification of Potential Biomarkers From Hepatocellular Carcinoma With MT1 Deletion

2021 ◽  
Vol 27 ◽  
Author(s):  
Ruohao Zhang ◽  
Miao Huang ◽  
Hong Wang ◽  
Shengming Wu ◽  
Jiali Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Independent Prognostic Factor ◽  
Comparative Genomic ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Cox Regression Analysis ◽  
Potential Biomarkers

Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Metallothioneins (MTs) are metal-binding proteins involved in multiple biological processes such as metal homeostasis and detoxification, as well as in oncogenesis. Copy number variation (CNV) plays a vital role in pathogenesis and carcinogenesis. Nevertheless, there is no study on the role of MT1 CNV in HCC.Methods: Array-based Comparative Genomic Hybridization (aCGH) analysis was performed to obtain the CNV data of 79 Guangxi HCC patients. The prognostic effect of MT1-deletion was analyzed by univariate and multivariate Cox regression analysis. The differentially expressed genes (DEGs) were screened based on The Gene Expression Omnibus database (GEO) and the Liver Hepatocellular Carcinoma of The Cancer Genome Atlas (TCGA-LIHC). Then function and pathway enrichment analysis, protein-protein interaction (PPI) and hub gene selection were applied on the DEGs. Lastly, the hub genes were validated by immunohistochemistry, tissue expression and prognostic analysis.Results: The MT1-deletion was demonstrated to affect the prognosis of HCC and can act as an independent prognostic factor. 147 common DEGs were screened. The most significant cluster of DEGs identified by Molecular Complex Detection (MCODE) indicated that the expression of four MT1s were down-regulated. MT1X and other five hub genes (TTK, BUB1, CYP3A4, NR1I2, CYP8B1) were associated with the prognosis of HCC. TTK, could affect the prognosis of HCC with MT1-deletion and non-deletion. NR1I2, CYP8B1, and BUB1 were associated with the prognosis of HCC with MT1-deletion.Conclusions: In the current study, we demonstrated that MT1-deletion can be an independent prognostic factor in HCC. We identified TTK, BUB1, NR1I2, CYP8B1 by processing microarray data, for the first time revealed the underlying function of MT1 deletion in HCC, MT1-deletion may influence the gene expression in HCC, which may be the potential biomarkers for HCC with MT1 deletion.

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