Identification of aberrantly methylated differentially expressed genes in breast cancer by integrated bioinformatics analysis

Yi, Lilan; Luo, Peng; Zhang, Jian

doi:10.1002/jcb.28904

Cited by 5 publications

(5 citation statements)

References 66 publications

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“…There are evidences that indicate identification of valuable biomarkers using transcriptomics 11 – 13 . Although some studies have revealed aberrant DNA methylation in GBM, limited research has been conducted on the comprehensive analysis of gene expression, methylation, and underlying molecular mechanisms 14 , 15 .…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation-based Diagnostic and Prognostic Biomarkers for Glioblastoma

et al. 2020

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Glioblastomas are the most common primary central nervous system malignancy tumor in adults. Glioblastoma patients have poor prognosis, with an average survival period of approximately 14 mo after diagnosis. To date, there are a limited number of effective treatment methods for glioblastoma, and its molecular mechanisms remain elusive. In this article, we analyzed the key biomarkers and pathways in glioblastoma patients based on gene expression and DNA methylation datasets. The 60 hypomethylated/upregulated genes and 110 hypermethylated/downregulated genes were identified in GSE50923, GSE50161, and GSE116520 microarrays. Functional enrichment analyses indicated that these methylated-differentially expressed genes were primarily involved in collagen fibril organization, chemical synaptic transmission, extracellular matrix-receptor interaction, and GABAergic synapse. The hub genes were screened from a protein–protein interaction network; in selected genes, increased NMB mRNA level was associated with favorable overall survival, while elevated CHI3L1, POSTN, S100A4, LOX, S100A11, IGFBP2, SLC12A5, VSNL1, and RGS4 mRNA levels were associated with poor overall survival in glioblastoma patients. Additionally, CHI3L1, S100A4, LOX, and S100A11 expressions were negatively correlated with their corresponding methylation status. Furthermore, the receiver-operator characteristic curve analysis indicated that CHI3L1, S100A4, LOX, and S100A11 can also serve as highly specific and sensitive diagnostic biomarkers for glioblastoma patients. Collectively, our study revealed the possible methylated-differentially expressed genes and associated pathways in glioblastoma and identified four DNA methylation-based biomarkers of glioblastoma. These results may provide insight on diagnostic and prognostic biomarkers, and therapeutic targets in glioblastoma.

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Section: Introductionmentioning

confidence: 99%

DNA Methylation-based Diagnostic and Prognostic Biomarkers for Glioblastoma

et al. 2020

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“…And Cai [ 10 ] use different data set to find the new hub gene CDCA5, which can change the cell cycle and make cells proliferate. In addition, many MDEGs are discussed in other systems, such as breast cancer, [ 11 ] osteosarcoma, [ 12 ] nasopharyngeal carcinoma, [ 13 ] and ovarian cancer. [ 14 ] Because the early symptoms are not obvious, most CCA patients have been diagnosed at the terminal stage.…”

Section: Discussionmentioning

confidence: 99%

Aberrantly methylated-differentially expressed genes and related pathways in cholangiocarcinoma

et al. 2022

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This study aimed to explore aberrantly methylated-differentially expressed genes and related pathways in cholangiocarcinoma (CCA). The mRNA expression data (GSE26566) and methylation profiling data (GSE44965) were collected from the Gene Expression Omnibus (GEO) Datasets. Differentially expressed genes and differentially methylated genes were identified using GEO2R. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using clusterprofiler in R. MCODE clustering tool was used to screen modules of the protein–protein interaction network in Cytoscape. Related pathways of hub gene by using gene set enrichment analysis. Eighty-one hypermethylated, lowly expressed genes (Hyper-LGs) and 76 hypomethylated, highly expressed genes (Hypo-HGs) were identified in this study. Hyper-LGs were enriched in ion channel binding and transcription factor activity, which was associated with Mineral absorption and Cell adhesion molecules. Hypo-HGs were enriched in cysteine-type endopeptidase activity, which was associated with Sphingolipid signaling pathway and T cell receptor signaling pathway. Based on protein–protein interaction networks, MYC and VWF were identified as hub genes for Hyper-LGs, and no hub genes for Hypo-HGs. This study found methylated-differentially expressed genes and signaling pathways that are connected with the CCA by using a series of bioinformatics databases and tools. MYC and VWF act as hub genes of CCA, which can be used as biomarkers based on aberrant methylation for the accurate diagnosis and treatment of CCA.

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“…23 DNA methylation biomarkers can be used as prognostic markers for the treatment of human cancers. 24 Therefore, exploring potential DNA methylation biomarkers is very important and urgently needed. In this study, differentially methylated CpG sites between breast cancer tissues and adjacent tissues were selected.…”

Section: Discussionmentioning

confidence: 99%

<p>HOPX Is an Epigenetically Inactivated Tumor Suppressor and Overexpression of HOPX Induce Apoptosis and Cell Cycle Arrest in Breast Cancer</p>

You¹,

Geng²,

Ye³

et al. 2020

OTT

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Background: Evidence has been shown that abnormal DNA methylation plays a vital role in the progression of breast cancer via silencing of gene expression. The results of bisulfite sequencing showed that the methylation status of HOPX in breast cancer tissues was higher than that in normal breast cancer tissues, but little known about the biological functions of HOPX in breast cancer. Methods: A total of 13 paired breast cancer and adjacent noncancerous tissues were subjected to bisulfite sequencing. Meanwhile, the methylation levels of cg218995965 and cg24862548 in breast cancer cells were detected by methylation-specific PCR (MSP). Flow cytometry, wound healing and transwell invasion assays were used to detect the apoptosis, migration and invasion in breast cancer cells. In addition, the expressions of HOPX, p21, cyclin D1 and CDK4 in cells were detected with Western blot assay. Results: Bisulfite sequencing indicated that the CpG sites (cg218995965 and cg24862548) in the HOPX promoter region showed significantly higher methylation in breast cancer tissues. In addition, methylation-specific PCR revealed that HOPX was significantly hypermethylated in breast cancer cell lines MDA-MB-468 and MCF-7. Furthermore, overexpression of HOPX significantly inhibited the proliferation of MDA-MB-468 and MCF-7 cells via inducing the apoptosis. Moreover, upregulation of HOPX markedly inhibited the migration and invasion abilities of MDA-MB-468 cells. Meanwhile, overexpression of HOPX obviously induced cell cycle arrest in MDA-MB-468 cells via upregulation of p21, and downregulation of cyclin D1 and CDK4. Additionally, overexpression of HOPX suppressed tumor growth of breast cancer in vivo. Conclusion: Our data showed that HOPX, a tumor suppressor, is epigenetically silenced in breast cancer. Overexpression of HOPX could suppress the progression of breast cancer, and thus indicating that it might serve as a potential target for the treatment of patients with breast cancer.

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Identification of aberrantly methylated differentially expressed genes in breast cancer by integrated bioinformatics analysis

Cited by 5 publications

References 66 publications

DNA Methylation-based Diagnostic and Prognostic Biomarkers for Glioblastoma

DNA Methylation-based Diagnostic and Prognostic Biomarkers for Glioblastoma

Aberrantly methylated-differentially expressed genes and related pathways in cholangiocarcinoma

<p>HOPX Is an Epigenetically Inactivated Tumor Suppressor and Overexpression of HOPX Induce Apoptosis and Cell Cycle Arrest in Breast Cancer</p>

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