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Using Integrated Bioinformatics Analysis to Identify Abnormally Methylated Differentially Expressed Genes in
Qing-Lian Chen1,2, Qian Yan1, Kun-Liang Feng1,2
1Guangzhou University of Chinese Medicine, Guangzhou, 510405, People's Republic of China.
Objective:
For the identification of abnormally methylated differentially expressed genes (MDEGs) in hepatocellular carcinoma (HCC), this study integrated four microarray datasets to investigate the fundamental mechanisms of tumorigenesis.
Methods:
We obtained the expression (GSE76427, GSE57957) and methylation (GSE89852, GSE54503) profiles from Gene Expression Omnibus (GEO). The abnormally MDEGs were identified by using R software. We used the clusterProfiler package for the functional and pathway enrichment analysis. The String database was used to build the protein-protein interaction (PPI) network and visualize it in Cytoscape. MCODE was employed in the module analysis. Additionally, Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) were employed to validate results. Lastly, we used cBioPortal software to examine the hub genetic alterations.
Results:
We identified 162 hypermethylated, down-regulated genes and 190 hypomethylated, up-regulated genes. Up-regulated genes with low methylation were enriched in biological processes, such as keratinocyte proliferation, and calcium homeostasis. Pathway analysis was enriched in the AMPK and PI3K-Akt signaling pathways. The PPI network identified PTK2, VWF, and ITGA2 as hypomethylated, high-expressing hub genes. Down-regulated genes with high methylation were related to responses to peptide hormones and estradiol, multi-multicellular organism process. Pathway analysis indicated enrichment in camp, oxytocin signaling pathways. The PPI network identified CFTR, ESR1, and CXCL12 as hypermethylated, low-expressing hub genes. Upon verification in TCGA databases, we found that the expression and methylation statuses of the hub genes changed significantly, and it was consistent with our results.
Conclusion:
The novel abnormally MDEGs and pathways in HCC were identified. These results helped us further understand the molecular mechanisms underlying HCC invasion, metastasis, and development. Hub genes can serve as biomarkers for an accurate diagnosis and treatment of HCC, and PTK2, VWF, ITGA2, CFTR, ESR1, and CXCL12 are included.
Insights
This study identified novel methylated differentially expressed genes (MDEGs) in hepatocellular carcinoma (HCC). Key hub genes like PTK2 and CFTR show potential as diagnostic and therapeutic biomarkers for HCC.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern with complex molecular underpinnings.
- Identifying differentially expressed genes (DEGs) associated with aberrant methylation is crucial for understanding HCC tumorigenesis.
Purpose of the Study:
- To identify abnormally methylated differentially expressed genes (MDEGs) in hepatocellular carcinoma (HCC).
- To investigate the molecular mechanisms of HCC tumorigenesis by integrating multi-omics data.
- To discover potential biomarkers for HCC diagnosis and treatment.
Main Methods:
- Integrated four microarray datasets for gene expression and methylation profiling.
- Utilized R software and bioinformatics packages (clusterProfiler, String, Cytoscape, MCODE) for MDEG identification, enrichment analysis, and network construction.
- Validated findings using Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases.
Main Results:
- Identified 162 hypermethylated/down-regulated and 190 hypomethylated/up-regulated genes in HCC.
- Hypomethylated, up-regulated genes were enriched in keratinocyte proliferation and calcium homeostasis pathways (e.g., AMPK, PI3K-Akt).
- Hypermethylated, down-regulated genes were associated with peptide hormone response and oxytocin signaling pathways. Hub genes identified include PTK2, VWF, ITGA2, CFTR, ESR1, and CXCL12.
Conclusions:
- Novel MDEGs and pathways critical for HCC development and progression were uncovered.
- The identified hub genes (PTK2, VWF, ITGA2, CFTR, ESR1, CXCL12) are significantly altered in HCC and validated in TCGA.
- These hub genes hold promise as potential biomarkers for accurate HCC diagnosis and targeted therapy.
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