Aberrant methylation of tumour suppressor genes WT1, GATA5 and PAX5 in hepatocellular carcinoma

Mzik, Martin; Chmelařová, Marcela; John, Stanislav; Laco, Ján; Slabý, Ondřej; Kiss, Igor; Bohovicová, Lucia; Palička, Vladimír; Nekvindová, Jana

doi:10.1515/cclm-2015-1198

Cited by 26 publications

(19 citation statements)

References 38 publications

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“…In our study we observed significantly higher methylation in three genes: GATA5, THBS1 and PAX5. GATA5 methylation has been already found in hepatocellular carcinoma 22 , colorectal cancer 23 , glioblastomas 24 and ovarian cancer 25 . THBS1 methylation has been demonstrated in laryngeal squamous cell carcinoma 26 , glioblastomas 24 and ovarian cancer 25 and PAX5 methylation has been shown in Table 2.…”

Section: Discussionmentioning

confidence: 93%

Elevated DNA methylation in malignant tumors of the sinonasal tract and its association with patient survival

Chmelařová¹,

Laco²,

Kovaříková³

et al. 2018

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Epigenetic modifications have been recognized as an important mechanism underlying carcinoma progression. DNA methylation plays an important role in cancer biology and represents potentially heritable changes in gene expression that do not involve DNA sequence. The aim of this study was to investigate promoter methylation of selected genes in sinonasal carcinoma by comparison with noncancerous sinonasal tissue. Methods. To search for epigenetic events (methylation in 25 tumor suppressor genes) we used MS-MLPA (Methylationspecific multiplex ligation-dependent probe amplification) to compare methylation status of 59 formalin fixed, paraffin embedded tissue samples of sinonasal carcinomas with 18 control samples. The most important changes in methylation were confirmed using MSP (Methylation specific PCR). Detected alterations in methylation were compared with clinicopathological characteristics. Results. Using a 20% cut-off for methylation (MS-MLPA), we found significantly higher methylation in GATA5 (P=0.0005), THSB1 (P=0.0002) and PAX5 (P=0.03) genes in the sinonasal cancer group compared to the control group. Methylation in five or more genes was associated with impaired overall survival (P=0.017). Conclusion. These findings provide evidence that alterations in methylation profile may be one of the major mechanisms in sinonasal carcinogenesis. In addition, changes in methylation could potentially be used as prognostic factors of sinonasal carcinoma and may have implications for future individualized therapy based on epigenetic changes.

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Section: Discussionmentioning

confidence: 93%

Elevated DNA methylation in malignant tumors of the sinonasal tract and its association with patient survival

Chmelařová¹,

Laco²,

Kovaříková³

et al. 2018

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…ID4 promoter methylation was also correlated with the risk of prostate cancer [44,45]. Meanwhile, NOL4, PAX6, TRIM58, and ZNF382 promoter methylation was also associated with the occurrence of many cancers [46][47][48][49][50][51][52][53][54][55]. Figure 4: Kaplan-Meier survival curves for overall survival outcomes according to the risk cuto point for prognostic hypermethylated/ hypomethylated genes.…”

Section: Discussionmentioning

confidence: 98%

Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma

Huang

et al. 2019

BioMed Research International

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Background. Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies due to its high morbidity and mortality. DNA methylation exerts a vital part in the development of PDAC. However, a mechanistic role of mutual interactions between DNA methylation and mRNA as epigenetic regulators on transcriptomic alterations and its correlation with clinical outcomes such as survival have remained largely uncovered in cancer. Therefore, elucidation of aberrant epigenetic alteration in the development of PDAC is an urgent problem to be solved. In this work, we conduct an integrative epigenetic analysis of PDAC to identify aberrant DNA methylation-driven cancer genes during the occurrence of cancer. Methods. DNA methylation matrix and mRNA profile were obtained from the TCGA database. The integration of methylation and gene expression datasets was analyzed using an R package MethylMix. The genes with hypomethylation/hypermethylation were further validated in the Kaplan–Meier analysis. The correlation analysis of gene expression and aberrant DNA methylation was also conducted. We performed a pathway analysis on aberrant DNG methylation genes identified by MethylMix criteria using ConsensusPathDB. Results. 188 patients with both methylation data and mRNA data were considered eligible. A mixture model was constructed, and differential methylation genes in normal and tumor groups using the Wilcoxon rank test was performed. With the inclusion criteria, 95 differential methylation genes were detected. Among these genes, 74 hypermethylation and 21 hypomethylation genes were found. The pathway analysis revealed an increase in hypermethylation of genes involved in ATP-sensitive potassium channels, Robo4, and VEGF signaling pathways crosstalk, and generic transcription pathway. Conclusion. Integrated analysis of the aberrant epigenetic alteration in pancreatic ductal adenocarcinoma indicated that differentially methylated genes could play a vital role in the occurrence of PDAC by bioinformatics analysis. The present work can help clinicians to elaborate on the function of differentially methylated expressed genes and pathways in PDAC. CDO1, GJD2, ID4, NOL4, PAX6, TRIM58, and ZNF382 might act as aberrantly DNA-methylated biomarkers for early screening and therapy of PDAC in the future.

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“…Another study revealed that DACT2 was repressed by promotor hypermethylation and pointed out the mediatory effect of DACT2 on papillary thyroid cancer proliferation and metastasis [8]. What is more, the aberrant promoter methylation of WT1, PAX5, PAX6, PY-CARD, and GATA5 was observed in hepatocellular carcinoma and the correlation of them with clinical parameters suggested their potential applications in cancer diagnosis [9]. Despite the fact that rare studies concentrated on the DNA hypomethylation regulation in cancer progression, there still exist some findings about gene activation caused by promotor hypomethymation, such as the overexpression of Bcl-2, Cyclin D2, and R-ras [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes in head and neck squamous cell carcinoma

Jin¹,

Qin

2020

Bioscience Reports

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DNA methylation has been demonstrated to play significant roles in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). In the present study, methylation microarray dataset (GSE87053) and gene expression microarray dataset (GSE23558) were downloaded from GEO database and analyzed through R language. A total of 255 hypermethylated-downregulated genes and 114 hypomethylated-upregulated genes were finally identified. Functional enrichment analyses were performed and a comprehensive protein–protein interaction (PPI) network was constructed. Subsequently, the top ten hub genes selected by Cytoscape software were subjected to further analyses. It was illustrated that the expression level of CSF2, CTLA4, ETS1, PIK3CD, and CFTR was intimately associated with HNSCC. Survival analysis suggested that CTLA4 and FGFR2 could serve as effective independent prognostic biomarkers for HNSCC patients. Overall, our study lay a groundwork for further investigation into the underlying molecular mechanisms in HNSCC carcinogenesis, providing potential biomarkers and therapeutic targets for HNSCC.

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Aberrant methylation of tumour suppressor genes WT1, GATA5 and PAX5 in hepatocellular carcinoma

Abstract: HCC evince aberrant promoter methylation of WT1, PAX5, PAX6, PYCARD and GATA5 genes. Correlation between GATA5, WT1 and PAX5 methylation and clinical/histological parameters is suggestive of applicability of these markers in non-invasive (epi)genetic testing in HCC.

Cited by 26 publications

References 38 publications

Elevated DNA methylation in malignant tumors of the sinonasal tract and its association with patient survival

Elevated DNA methylation in malignant tumors of the sinonasal tract and its association with patient survival

Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma

Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes in head and neck squamous cell carcinoma

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