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

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.

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Co-expression Network Identification and Clinical Prognostic Evaluation of Hub Genes in Head and Neck Squamous Cell Carcinoma

10.21203/rs.3.rs-77378/v1 ◽

2020 ◽

Author(s):

Jialian Feng ◽

Baoai Han ◽

Chaosheng Yu ◽

Congxiang Shen ◽

Zhong Wen

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Transcriptional Level ◽

Hub Genes ◽

Poor Prognostic Factor ◽

Potential Biomarker

Abstract Background: According to statistics, even with active treatment, the recurrence rate of HNSCC is at 40%-50%. Head and neck cancer remains a challenge for otolaryngologists. Therefore, the identification of new biomarkers is an urgent need for the diagnosis, treatment, and prognosis of malignant tumors of the head and neck. Methods: In this study, transcriptome data from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules and hub genes related to head and neck squamous cell carcinoma (HNSCC). Protei-Protei interaction(PPI) network and Cytoscape software were used to analyze the protein interaction network. HNSCC clinical data from the TCGA and Gene Expression Profile Interactive Analysis 2 databases were used to analyze the survival rate of hub genes, and the correlation between hub genes and tumor stage was further analyzed.Results: A total of 2836 and 570 DEGs were identified from the TCGA expression data and GEO gene chip datasets, respectively. We found that the green module had the highest correlation with HNSCC. A total of 15 hub genes were also identified. In the Human Protein Atlas database, we found that thioredoxin reductase 1 (TXNRD1) was overexpressed in HNSCC tumors compared with normal tissues at the transcriptional level. Survival analysis also suggested that TXNRD1 was a poor prognostic factor for HNSCC.Conclusion: Our results indicate that TXNRD1 is very likely to be identified as a potential biomarker and target for HNSCC. However, further research is required to fully reveal its role in HNSCC pathogenesis as well as its value as a prognostic biomarker.

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Functional Genomics Screen with Pooled shRNA Library and Gene Expression Profiling with Extracts of Azadirachta indica Identify Potential Pathways for Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

10.1101/381749 ◽

2018 ◽

Author(s):

Neeraja M Krishnan ◽

Hiroto Katoh ◽

Vinayak Palve ◽

Manisha Pareek ◽

Reiko Sato ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cancer Cell ◽

Squamous Cell ◽

Azadirachta Indica ◽

Neck Squamous Cell Carcinoma ◽

Neem Extract ◽

Infected Cells

AbstractTumor suppression by the extracts of Azadirachta indica (neem) works via anti-proliferation, cell cycle arrest, and apoptosis, demonstrated previously using cancer cell lines and live animal models. However, very little is known about the molecular targets and pathways that the neem extracts and the associated compounds act through. Here, we address this using a genome-wide functional pooled shRNA screen on head and neck squamous cell carcinoma cell line treated with crude neem leaf extracts, known for their anti-tumorigenic activity. By analyzing differences in global clonal sizes of the shRNA-infected cells cultured under no treatment and treatment with neem leaf extract conditions, assayed using next-generation sequencing, we found 225 genes affected the cancer cell growth in the shRNA-infected cells treated with neem extract. Pathway enrichment analyses of whole-genome gene expression data from cells temporally treated with neem extract revealed important roles played by the TGF-β pathway and HSF-1-related gene network. Our results indicate that neem extract simultaneously affects various important molecular signaling pathways in head and neck cancer cells, some of which may be therapeutic targets for this devastating tumor.

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Identification of potential core genes and pathways predicting pathogenesis in head and neck squamous cell carcinoma

Bioscience Reports ◽

10.1042/bsr20204148 ◽

2021 ◽

Author(s):

Mengmeng Wang ◽

Bin Zhong ◽

Man Li ◽

Yanjuan Wang ◽

Huaian Yang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Small Molecules ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Potential Drug ◽

Hub Genes ◽

Potential Core ◽

Hnscc Cell

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.

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Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

Frontiers in Oncology ◽

10.3389/fonc.2020.582827 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yang Yang ◽

Jaeil Ahn ◽

Rekha Raghunathan ◽

Bhaskar V. Kallakury ◽

Bruce Davidson ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Hpv Infection ◽

Neck Squamous Cell Carcinoma ◽

Therapeutic Interventions ◽

Tumor Tissues ◽

Significant Difference

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.

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The Identification of Stemness-Related Genes in the Risk of Head and Neck Squamous Cell Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.688545 ◽

2021 ◽

Vol 11 ◽

Author(s):

Guanying Feng ◽

Feifei Xue ◽

Yingzheng He ◽

Tianxiao Wang ◽

Hua Yuan

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Network Analysis ◽

Cell Carcinoma ◽

Head And Neck ◽

Risk Score ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Potential Biomarker ◽

Score Model

ObjectivesThis study aimed to identify genes regulating cancer stemness of head and neck squamous cell carcinoma (HNSCC) and evaluate the ability of these genes to predict clinical outcomes.Materials and MethodsThe stemness index (mRNAsi) was obtained using a one-class logistic regression machine learning algorithm based on sequencing data of HNSCC patients. Stemness-related genes were identified by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis (LASSO). The coefficient of LASSO was applied to construct a diagnostic risk score model. The Cancer Genome Atlas database, the Gene Expression Omnibus database, Oncomine database and the Human Protein Atlas database were used to validate the expression of key genes. Interaction network analysis was performed using String database and DisNor database. The Connectivity Map database was used to screen potential compounds. The expressions of stemness-related genes were validated using quantitative real‐time polymerase chain reaction (qRT‐PCR).ResultsTTK, KIF14, KIF18A and DLGAP5 were identified. Stemness-related genes were upregulated in HNSCC samples. The risk score model had a significant predictive ability. CDK inhibitor was the top hit of potential compounds.ConclusionStemness-related gene expression profiles may be a potential biomarker for HNSCC.

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