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

Jili Cui,Miaomiao Xue,Lian Zheng,Yuanyuan Zhang

doi:10.1038/s41598-021-81971-5

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.

Highlights

High levels of DNMT1 expression are associated with poor clinical p rognosis[18].it is reported that upregulation of DNMT1 functions in tumor-suppressor gene a ctivation[19,20]
We performed a pan-cancer analysis of DNMT1 expression, and we found that DNMT1 was upregulated in several different tumor types (Fig. 1A)
Results showed that DNMT1 protein expression was significantly overexpressed in Head and neck squamous cell carcinoma (HNSCC) tissues compared with normal tissue (Fig. 1C)

Summary

Introduction

High levels of DNMT1 expression are associated with poor clinical p rognosis[18].it is reported that upregulation of DNMT1 functions in tumor-suppressor gene a ctivation[19,20]. We utilized the bioinformation analysis and validated the characters of m5C related regulators in HNSCC, and DNMT1 functioned as a key regulator in HNSCC p rogression[22]. We identified that DNMT1 might serve as a crucial m5C regulator in malignant activities of HNSCC, and increased DNMT1 expression was associated with patient’s mortality rate[22]. The comprehensively biological activities of DNMT1 in HNSCC tumorigenesis and progression has not yet been clarified. We used public databases and online analysis websites to unravel the role of DNMT1 in HNSCC tumorigenesis and progression. We identified methylation markers with diagnostic potential, and identified potential targets for the treatment of HNSCC

Methods

Results

Conclusion