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Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignancy in the world. DNA cytosine-5-methyltransferase 1 (DNMT1) play key roles in carcinogenesis and regulation of the immune micro-environment, but the gene expression and the role of DNMT1 in HNSCC is unknown. In this study, we utilized online tools and databases for pan-cancer and HNSCC analysis of DNMT1 expression and its association with clinical cancer characteristics. We also identified genes that positively and negatively correlated with DNMT1 expression and identified eight hub genes based on protein-protein interaction (PPI) network analysis. Enrichment analyses were performed to explore the biological functions related with of DNMT1. The Tumor Immune Estimation Resource (TIMER) database was performed to explore the relationship between DNMT1 expression and immune-cell infiltration. We demonstrated that DNMT1 gene expression was upregulated in HNSCC and associated with poor prognosis. Based on analysis of the eight hub genes, we determined that DNMT1 may be involved in cell cycle, proliferation and metabolic related pathways. We also found that significant difference of B cells infiltration based on TP 53 mutation. These findings suggest that DNMT1 related epigenetic alterations have close relationship with HNSCC progression, and DNMT1 could be a novel diagnostic biomarker and a promising therapeutic target for HNSCC.

SUBMITTER: Cui J

PROVIDER: S-EPMC7838186 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis.

Cui Jili J Zheng Lian L Zhang Yuanyuan Y Xue Miaomiao M

Scientific reports 20210126 1

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignancy in the world. DNA cytosine-5-methyltransferase 1 (DNMT1) play key roles in carcinogenesis and regulation of the immune micro-environment, but the gene expression and the role of DNMT1 in HNSCC is unknown. In this study, we utilized online tools and databases for pan-cancer and HNSCC analysis of DNMT1 expression and its association with clinical cancer characteristics. We also identified genes that positivel ...[more]

PMID: 33500531

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Project description:BackgroundPLEK2 (pleckstrin) could bind to membrane-bound phosphatidylinositols and further promote cell spread. Recently, several studies have noted the importance of PLEK2 in tumor metastasis. However, the role of PLEK2 in head and neck squamous cell carcinoma (HNSCC) remains to be elucidated.MethodsThe PLEK2 expression in HNSCC was identified using Oncomine, Gene Expression Omnibus (GEO), UALCAN databases, and western blot analysis. Prognosis analysis was performed using Kaplan-Meier plotter, DriverDBv3, UALCAN, UCSC Xena, and GEO databases. Single-cell functional analysis was further performed using the cancerSEA database. The PLEK2-related co-expressed genes were identified, and gene set enrichment analysis was performed using LinkedOmics. Furthermore, the top 10 hub genes were identified using the cytoHubba plug-in of Cytoscape. Then, gene enrichment analysis, pathway activity, and drug sensitivity analyses of the hub genes were performed using the R package "clusterProfiler" and GSCAlite. Finally, the UCSC Xena browser was utilized to explore the hub gene most likely to play a synergic role with PLEK2 in HNSCC.ResultsElevated expression of PLEK2 was observed in HNSCC and even in HNSCC subgroups based on diverse clinicopathological features, portending a poor prognosis in HNSCC. PLEK2 was correlated with metastasis and hypoxia in HNSCC, and the PLEK2-related co-expressed genes were mainly involved in the focal adhesion pathway. The top 10 hub genes were primarily enriched in focal adhesion, HPV infection, ECM-receptor interaction, and PI3K-AKT signaling pathway, and epithelial-mesenchymal transition pathway was activated. Furthermore, the expression levels of the hub genes were associated with sensitivity and resistance to various small molecules and anti-cancer drugs. Further study suggested that ITGA3 and PLEK2 might be viewed as inextricably linked in facilitating HNSCC metastasis.ConclusionsIn general, PLEK2 might serve as a potential biomarker for the diagnosis of HNSCC and guide the development of targeted therapies for HNSCC.

Dataset Information

Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis.

Publications

Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis.

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