scholarly journals HLF is a Potential Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma Based on Bioinformatic Analysis and Experimental Validation

Author(s):  
Wei Fang ◽  
Di Wan ◽  
Jun Chen ◽  
Weiqun Ma ◽  
Zhen Luo ◽  
...  

Abstract BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers worldwide, with an increasing incidence. However, the underlying molecular mechanisms of HNSCC are poorly understood.MethodIn this work, 5 original datasets (GSE23558, GSE13601, GSE30784, GSE9844, GSE78060) of Head and neck squamous cell carcinoma (HNSCC) were selected from Gene Expression Omnibus (GEO) database. To identify differentially expressed genes (DEGs) in HNSCC and adjacent tissues. The common DEGs were acquired by Venn diagram. The sensitivity and specificity of HLF were determined by Receiver operating characteristic curves (ROC). Then, In order to further confirm the relationship between HLF and HNSCC patient’s prognosis, the expression and survival analysis of HLF was performed by Gene Expression Profiling Interactive Analysis (GEPIA), Cell culture, reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunohistochemical staining.ResultsSeventeen DEGs were screened from five sets of HNSCC functional gene expression series in GEO datasets. The low expression of HLF was indicated might be correlated with poor prognosis of HNSCC patients based on the bioinformatics analysis. According to the results of Cell culture, RT-PCR, western blotting, immunohistochemical staining, it was confirmed that the low level of HLF expression correlated with poor prognosis of HNSCC patients.ConclusionThe study effectively revealed useful information about the relationship of the low level of HLF expression and HNSCC. In summary, we identified HLF as a potential prognostic biomarker and therapeutic target for HNSCC.

2020 ◽  
Author(s):  
Wei Fang ◽  
Di Wan ◽  
Jun Chen ◽  
Weiqun Ma ◽  
Zhen Luo ◽  
...  

Abstract BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers worldwide, with an increasing incidence. However, the underlying molecular mechanisms of HNSCC are poorly understood.MethodIn this work, 5 original datasets (GSE23558, GSE13601, GSE30784, GSE9844, GSE78060) of Head and neck squamous cell carcinoma (HNSCC) were selected from Gene Expression Omnibus (GEO) database. To identify differentially expressed genes (DEGs) in HNSCC and adjacent tissues. The common DEGs were acquired by Venn diagram. The sensitivity and specificity of HLF were determined by Receiver operating characteristic curves (ROC). Then, In order to further confirm the relationship between HLF and HNSCC patient’s prognosis, the expression and survival analysis of HLF was performed by Gene Expression Profiling Interactive Analysis (GEPIA), Cell culture, reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunohistochemical staining.ResultsSeventeen DEGs were screened from five sets of HNSCC functional gene expression series in GEO datasets. The low expression of HLF was indicated might be correlated with poor prognosis of HNSCC patients based on the bioinformatics analysis. According to the results of Cell culture, RT-PCR, western blotting, immunohistochemical staining, it was confirmed that the low level of HLF expression correlated with poor prognosis of HNSCC patients.ConclusionThe study effectively revealed useful information about the relationship of the low level of HLF expression and HNSCC. In summary, we identified HLF as a potential prognostic biomarker and therapeutic target for HNSCC.


2021 ◽  
Vol 20 ◽  
pp. 153303382110458
Author(s):  
Jing Sun ◽  
Guiqing Fang ◽  
Zhibin Zuo ◽  
Xijiao Yu ◽  
Lande Xue ◽  
...  

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with poor prognosis and immune response, which plays an important role in tumor progression. Recently, immunotherapies have revolutionized the therapeutic means of malignancies including HNSCC. However, the relationship between immunophenotypes of HNSCC and its clinical response to immune-checkpoint inhibitors remains unclear. We aim to identify molecular subtyping related to distinct immunophenotypes in HNSCC. Consensus clustering algorithm was conducted for subtyping. Immunophenotypes between subtypes were compared according to infiltrating immunocytes, immune reactions, major histocompatibility complex (MHC) family, immunoinhibitory, immunostimulatory and immune scores. The relationship between immunophenotype and genotype was investigated from gene mutation and tumor mutation burden. The potential response of Immune-checkpoint blockade (ICB) therapy was estimated with TIDE and ImmuCellAI algorithms, and immune-checkpoint genes. The immune characteristics were also investigated. Biological functions were annotated by the gene-set enrichment analysis (GSEA) algorithm. Two distinct immune subtypes of HNSCC with different survival outcomes, biological characteristics, immunophenotype, and ICB response were identified. The subtype-1 was featured with better prognosis, more infiltrated immunocytes, stronger immune reaction, higher immune-related gene expression, higher immune-checkpoint gene expression (PD-1, PD-L1, and CTLA-4), and better ICB response. A higher immune response in subtype-1 was also revealed by GSEA. Subtype-1 possessed a higher immune response and more sensitivity to ICB therapy leading to a better prognosis. These findings may shed promising light on the immunotherapy strategy in HNSCC


2021 ◽  
Author(s):  
Ruoya Wang

AbstractHead and neck squamous cell carcinoma (HNSCC) is a high mortality disease. Extension of long-chain fatty acid family member 6 (ELOVL6) is a key enzyme involved in fat formation that catalyzes the elongation of saturated and monounsaturated fatty acids. Overexpression of ELOVL6 has been associated with obesity-related malignancies, including hepatocellular carcinoma, breast, colon, prostate, and pancreatic cancer. The following study investigated the role of ELOVL6 in HNSCC patients. Gene expression and clinicopathological analysis, enrichment analysis, and immune infiltration analysis were based on the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA), with additional bioinformatics analyses. The statistical analysis was conducted in R, and TIMER was used to analyze the immune response of ELOVL6 expression in HNSCC. The expression of ELOVL6 was related to tumor grade. Survival analysis showed that patients with high expression of ELOVL6 had a poor prognosis. Moreover, the results of GSEA enrichment analysis showed that ELOVL6 affects the occurrence of HNSCC through fatty acid metabolism, biosynthesis of unsaturated fatty acids, and other pathways. Finally, ELOVL6 verified by the Human Protein Atlas (HPA) database were consistent with the mRNA levels in HNSCC samples. ELOVL6 is a new biomarker for HNSCC that may be used as a potential predictor of the prognosis of human HNSCC.


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.


Head & Neck ◽  
2011 ◽  
Vol 33 (2) ◽  
pp. 267-273 ◽  
Author(s):  
Claude A. Fischer ◽  
Minoa Jung ◽  
Inti Zlobec ◽  
Edith Green ◽  
Claudio Storck ◽  
...  

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.


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.


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