scholarly journals Identification of Hub Genes Associated With Development of Head and Neck Squamous Cell Carcinoma by Integrated Bioinformatics Analysis

2020 ◽  
Vol 10 ◽  
Author(s):  
Chia Ying Li ◽  
Jia-Hua Cai ◽  
Jeffrey J. P. Tsai ◽  
Charles C. N. Wang
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jili Cui ◽  
Lian Zheng ◽  
Yuanyuan Zhang ◽  
Miaomiao Xue

AbstractHead 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.


2021 ◽  
Author(s):  
Mengmeng Wang ◽  
Bin Zhong ◽  
Man Li ◽  
Yanjuan Wang ◽  
Huaian Yang ◽  
...  

Head and neck squamous cell carcinoma (HNSCC) is the most common subtype of head and neck cancer; however, its pathogenesis and potential therapeutic targets remain largely unknown. In this study, we analyzed three gene expression profiles and screened differentially expressed genes (DEGs) between HNSCC and normal tissues. The DEGs were subjected to gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), protein–protein interaction (PPI), and survival analyses, while the connectivity map (CMap) database was used to predict candidate small molecules that may reverse the biological state of HNSCC. Finally, we measured the expression of the most relevant core gene in vitro and examined the effect of the top predicted potential drug against the proliferation of HNSCC cell lines. Among the 208 DEGs and ten hub genes identified, CDK1 and CDC45 were associated with unfavorable HNSCC prognosis, and three potential small molecule drugs for treating HNSCC were identified. Increased CDK1 expression was confirmed in HNSCC cells, and menadione, the top predicted potential drug, exerted significant inhibitory effects against HNSCC cell proliferation and markedly reversed CDK1 expression. Together, the findings of this study suggest that the ten hub genes and pathways identified may be closely related to HNSCC pathogenesis. In particular, CDK1 and CDC45 overexpression could be reliable biomarkers for predicting unfavorable prognosis in patients with HNSCC, while the new candidate small molecules identified by CMap analysis provide new avenues for the development of potential drugs to treat HNSCC.


Author(s):  
Yi Ding ◽  
Min Li ◽  
Tuersong Tayier ◽  
Long Chen ◽  
ShuMei Feng

Background: : Head and neck squamous cell carcinoma (HNSCC) is a common cancer that is characterized by a complex pathogenesis. Only limited data are available on the primary pathogenic genes and pathways in HNSCC. Objective: This study aimed to identify potential biomarkers of HNSCC and explore its underlying mechanisms. Methods: We screened differentially expressed genes (DEGs) using the Gene Expression Omnibus(GEO) database. Gene Ontology (GO) and Reactome pathway enrichment were analyzed using the STRING database. The protein-protein interaction network of the DEGs was reconstructed using Cytoscape software in STRING. The ONCOMINE and UNLCAN databases were used to identify the expression of hub genes. In addition, we employed UNLCAN to correlate tumor grade with key genes. Results: Finally, the effect of hub genes on overall survival (OS) was analyzed using the Kaplan-Meier method. In total, 22 DEGs were identified, These were related to the mitotic cell cycle, mitotic G1-G1, and S phases, G2/M transition, NOTCH signaling, and regulation of TP53 activity. Seven hub genes were screened with Cytoscape. Increased expression of five hub genes (AURKA, BIRC5, MKI67, UBE2C, and TOP2A) was related to a higher tumor grade and worse OS. Conclusion: We have identified five key genes that may help us understand the carcinogenic mechanisms related to the cell cycle in HNSCC. These genes may be used as biomarkers for survival and treatment of HNSCC.


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