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

2021 ◽  
Vol 11 ◽  
Author(s):  
Guanying Feng ◽  
Feifei Xue ◽  
Yingzheng He ◽  
Tianxiao Wang ◽  
Hua Yuan

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.

2020 ◽  
Author(s):  
Jialian Feng ◽  
Baoai Han ◽  
Chaosheng Yu ◽  
Congxiang Shen ◽  
Zhong Wen

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.


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.


2018 ◽  
Author(s):  
Neeraja M Krishnan ◽  
Hiroto Katoh ◽  
Vinayak Palve ◽  
Manisha Pareek ◽  
Reiko Sato ◽  
...  

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.


2019 ◽  
Vol 121 ◽  
pp. 210-223 ◽  
Author(s):  
Charlotte Lecerf ◽  
Maud Kamal ◽  
Sophie Vacher ◽  
Walid Chemlali ◽  
Anne Schnitzler ◽  
...  

2019 ◽  
Vol 8 (12) ◽  
pp. 2041 ◽  
Author(s):  
Irimie-Aghiorghiesei ◽  
Pop-Bica ◽  
Pintea ◽  
Braicu ◽  
Cojocneanu ◽  
...  

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies with serious impact on patient quality of life due to a reduced rate of response to chemotherapy or radiation therapy. MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that upregulated miR-21 could serve as a potential biomarker for human cancer diagnosis. Considering the target genes identified for miR-21 in HNSCC, this transcript is an important player in several cellular processes that control carcinogenesis. The abnormal expression of miR-21 in this group of pathologies has been assessed in several publications, but given the heterogeneity of the published results, a meta-analysis and proper bioinformatics analysis of expression databases are needed to correctly establish the prognostic potential of this molecule. The present meta-analysis comprises the published survival data on HNSCC patients, reported as HR and 95% CI, in association with the expression levels of miR-21. Our investigation revealed that miR-21 could be used successfully as a prognostic biomarker in HNSCC patients, confirming its oncogenic potential. Specifically, the upregulation of miR-21 in these patients predicts a worse outcome in terms of survival rate.


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