Bioinformatics-based discovery of PYGM and TNNC2 as potential biomarkers of head and neck squamous cell carcinoma

Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality rates and ranks as the sixth most common cancer all over the world. Despite numerous advancements in therapeutic methods, the prognosis of HNSCC patients still remains poor. Therefore, there is an urgent need to have a better understanding of the molecular mechanisms underlying HNSCC progression and to identify essential genes that could serve as effective biomarkers and potential treatment targets. In the present study, original data of three independent datasets were downloaded from the Gene Expression Omnibus database (GEO) and R language was applied to screen out the differentially expressed genes (DEGs). PYGM and TNNC2 were finally selected from the overlapping DEGs of three datasets for further analyses. Transcriptional and survival data related to PYGM and TNNC2 was detected through multiple online databases such as Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioportal, and UALCAN. Quantitative real-time polymerase chain reaction (qPCR) analysis was adopted for the validation of PYGM and TNNC2 mRNA level in HNSCC tissues and cell lines. Survival curves were plotted to evaluate the association of these two genes with HNSCC prognosis. It was demonstrated that PYGM and TNNC2 were significantly down-regulated in HNSCC and the aberrant expression of PYGM and TNNC2 were correlated with HNSCC prognosis, implying the potential of exploiting them as therapeutic targets for HNSCC treatment or potential biomarkers for diagnosis and prognosis.

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Tumor microenvironment and immune evasion in head and neck squamous cell carcinoma

International Journal of Oral Science ◽

10.1038/s41368-021-00131-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Areeg Elmusrati ◽

Justin Wang ◽

Cun-Yu Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Immune System ◽

Tumor Microenvironment ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

High Morbidity ◽

Advanced Therapies

AbstractHead and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.

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

Scientific Reports ◽

10.1038/s41598-021-81971-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jili Cui ◽

Lian Zheng ◽

Yuanyuan Zhang ◽

Miaomiao Xue

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Immune Cell ◽

Neck Squamous Cell Carcinoma ◽

Hub Genes ◽

Significant Difference ◽

Dnmt1 Expression

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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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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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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