Dataset Information

A transcriptomic analysis based on aberrant methylation levels revealed potential novel therapeutic targets for nasopharyngeal carcinoma.

ABSTRACT:

Background

This study aimed to identify potential novel therapeutic targets for nasopharyngeal carcinoma (NPC) by identifying aberrantly methylated-differentially expressed genes (DEGs) and pathways based on a comprehensive bioinformatics analysis.

Methods

Eight gene expression data sets and 2 methylation microarray data sets that included NPC and control groups from the Gene Expression Omnibus were identified. Meta-analyses of the DEGs were performed using the online analysis database "NetworkAnalyst". Aberrantly methylated gene loci were obtained from the GEO2R. Aberrantly methylated DEGs were obtained from Venn diagrams. The enrichment analysis was carried out on the "Metascape" website, and the protein-protein interaction (PPI) network construction, network analysis, and visualization of the analysis results were carried out on the "String" website using "Cytoscape" software.

Results

In total, 544 hypomethylation high-expression genes and 164 hypermethylation low-expression genes were obtained. The enrichment and PPI network analyses suggested that several pathways and hub genes with abnormal gene expression accompanied by methylation change, including inositol-trisphosphate 3-kinase B (ITPKB), G protein subunit beta 5 (GNB5), FYN proto-oncogene, Src family tyrosine kinase (FYN), LCK proto-oncogene, Src family tyrosine kinase (LCK), nuclear factor of activated T cells 1 (NFATC1), GNAS complex locus (GNAS), protein kinase C beta (PRKCB), zeta chain of T cell receptor associated protein kinase 70 (ZAP70), lysophosphatidic acid receptor 1 (LPAR1), protein kinase C epsilon (PRKCE), tumor protein p53 (TP53), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fibronectin 1 (FN1), cyclin D1 (CCND1), vascular endothelial growth factor A (VEGFA), HRas proto-oncogene, GTPase (HRAS), signal transducer and activator of transcription 3 (STAT3), fibroblast growth factor 2 (FGF2), amyloid beta precursor protein (APP), and matrix metallopeptidase 2 (MMP2), may be related to the occurrence of nasopharyngeal carcinoma .

Conclusions

The identification of novel and important pathways and hub genes and their roles in the occurrence and development of NPC will guide clinical research and the development of pharmaceutical targets.

SUBMITTER: Lyu M

PROVIDER: S-EPMC8848444 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

A transcriptomic analysis based on aberrant methylation levels revealed potential novel therapeutic targets for nasopharyngeal carcinoma.

Lyu Mo M Yi Xinzhu X Huang Zhiwei Z Chen Yirong Y Ai Zhu Z Liang Yuying Y Feng Qili Q Xiang Zhiming Z

Annals of translational medicine 20220101 2

<h4>Background</h4>This study aimed to identify potential novel therapeutic targets for nasopharyngeal carcinoma (NPC) by identifying aberrantly methylated-differentially expressed genes (DEGs) and pathways based on a comprehensive bioinformatics analysis.<h4>Methods</h4>Eight gene expression data sets and 2 methylation microarray data sets that included NPC and control groups from the Gene Expression Omnibus were identified. Meta-analyses of the DEGs were performed using the online analysis dat ...[more]

PMID: 35282089

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Project description:Background: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy. Large-scale genetics or epigenetics studies of NPC have been relatively scarce and sporadic, and there are no effective targeted drugs for NPC. Integrative analysis of multiple different omics profiles has been proved to be an effective approach to shed new light on cancer. Methods: We developed a pipeline to aggregate consensus differentially expressed genes (DEGs) from multiple expression datasets from different platforms. Integrated bioinformatics analysis of DNA methylation and gene expression was used to prioritize key genes in NPC. We explored the biological and clinical importance of key genes, combining differential co-expression analysis, network analysis of protein-protein and microRNA (miRNA)-target interactions, and pan-cancer survival analysis. Results: We obtained 668 upregulated and 594 downregulated consensus DEGs, which enriched in the PI3K-AKT, NF-κB and immune-related pathways. In NPC, 98% of 3364 differentially methylated sites were hypermethylated. Actively expressed EBV gene EBNA1 was positively correlated with over-expressed genes coding DNA methyltransferase and Polycomb group proteins, suggesting that EBV infection may have an important role in the hypermethylation of NPC. Through integrated analysis of DNA methylation and mRNA and miRNA expression profiles, we prioritized 56 hypermethylated downregulated genes, including 7 tumor suppressor genes, and constructed a miRNA-target regulation network consisting of 12 hypermethylated miRNAs and 25 upregulated oncogenes. The promoter hypermethylation of PRKCB causing its downregulation was validated by experimental results and higher PRKCB expression was associated with longer overall survival in head-neck squamous cell carcinoma, suggesting the potential of PRKCB as a promising disease biomarker for NPC. Conclusions: Our integrative analysis provides reliable key genes for candidate biomarkers for diagnosis and prognosis in NPC. Based on the combined evidence of promoter hypermethylation, expression up-regulation, and association with overall survival, genes such as SCUBE2, PRKCB, IKZF1, MAP4K1, and GATA6 could be promising novel diagnostic biomarkers, and miRNAs including MIR150, MIR152, and MIR34 could be candidate prognosis biomarkers.

Project description:BackgroundNon-alcoholic steatohepatitis (NASH) is the most prevalent chronic liver condition globally, with potential progression to cirrhosis, and even hepatocellular carcinoma (HCC). The increasing prevalence of NASH underscores the urgent need for advanced diagnostic and therapeutic strategies. Despite its widespread impact, effective treatments to prevent the progression of NASH remain elusive, highlighting the critical importance of innovative molecular techniques in both the diagnosis and management of this disease.MethodsSix microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs).We identified 62 robust upregulated genes and 24 robust downregulated genes. These genes were undergone Gene Ontology enrichment analysis and further examination for expression correlation with NAS score. Molecular subtypes were generated using "ConsensusClusterPlus" on identified genes, which were further assessed for tumor stage relevance, expression differences in adjacent and tumor tissues, and impact on survival in TCGA liver cancer patients. Single-cell analysis was then used to explore the genes across different cell types and subgroups as well as cell-type interactions. The clinical utility of predicted core genes was highlighted through decision curve analysis, with emphasis on HCC prognosis. The GDSC database was used to evaluate the relationship between the predicted core genes and drug sensitivity, while the TIDE database was used to evaluate their relationship with immunotherapy.ResultsFour core genes, TREM2, GDF15, TTC39A, and ANXA2, were identified as key to influencing HCC prognosis and therapy responsiveness, especially immune treatment efficacy in NASH-associated HCC.ConclusionThe core genes may act as critical biomarkers driving the progression of NASH to HCC. They are potential novel targets for the diagnosis and treatment of NASH progression, offering innovative perspectives for its clinical management.

Dataset Information

A transcriptomic analysis based on aberrant methylation levels revealed potential novel therapeutic targets for nasopharyngeal carcinoma.

Background

Methods

Results

Conclusions

Publications

A transcriptomic analysis based on aberrant methylation levels revealed potential novel therapeutic targets for nasopharyngeal carcinoma.

Similar Datasets

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