scholarly journals Identification of Expression Patterns and Potential Prognostic Significance of m5C-Related Regulators in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhenyuan Han ◽  
Biao Yang ◽  
Yu Wang ◽  
Xiuxia Zeng ◽  
Zhen Tian
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Critical Role ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Differentially Expressed ◽  
Rna Modification

5-Methylcytosine (m5C) methylation is a major epigenetic technique of RNA modification and is dynamically mediated by m5C “writers,” “erasers,” and “readers.” m5C RNA modification and its regulators are implicated in the onset and development of many tumors, but their roles in head and neck squamous cell carcinoma (HNSCC) have not yet been completely elucidated. In this study, we examined expression patterns of core m5C regulators in the publicly available HNSCC cohort via bioinformatic methods. The differentially expressed m5C regulators could divide the HNSCC cohort into four subgroups with distinct prognostic characteristics. Furthermore, a three-gene expression signature model, comprised of NSUN5, DNMT1, and DNMT3A, was established to identify individuals with a high or low risk of HNSCC. To explore the underlying mechanism in the prognosis of HNSCC, screening of differentially expressed genes, followed by the analysis of functional and pathway enrichment, from individuals with high- or low-risk HNSCC was performed. The results revealed a critical role for m5C RNA modification in two aspects of HNSCC: (1) dynamic m5C modification contributes to the regulation of HNSCC progression and (2) expression patterns of NSUN5, DNMT1, and DNMT3A help to predict the prognosis of HNSCC.

scholarly journals An Immune-associated lncRNA Signature Predicts the Survival of Patients With Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Jian Wang ◽  
Qinjiang Bian ◽  
Jialin Liu ◽  
Lijuan Du ◽  
Adili Moming
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Operating Characteristic ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Differentially Expressed ◽  
Risk Scores

Abstract BackgroundThe malignant progression and treatment resistance of head and neck squamous cell carcinoma are closely related to the tumor immune microenvironment. Long non-coding RNA (lncRNA) plays a regulatory role in this process and may be exploited as new signatures for head and neck squamous cell carcinoma(HNSCC) diagnosis, prognosis, and treatment.MethodsHNSCC transcriptome data was abstracted from the Cancer Genome Atlas (TCGA) data resource, and uncovered immune-linked lncRNA through co-expression analysis. Besides, univariate along with Lasso penalty regression were employed to determine immune-linked lncRNA pairs with different expressions. We then compared area under the curve, calculated the Akaike information criterion (AIC) value of the receiver operating characteristic curve for 5 years, determined cutoff points, and established an optimal predictive model for identifying high- and low-risk HNSCC patients. Then, we evaluated these patients with high- and low-risk HNSCC in terms of survival, clinic-pathological characteristics, tumor-infiltrating immune cells, chemotherapeutic efficacy, and immunosuppressed biomarkers.ResultsThis study included 545 samples. By co-expression analysis of known immune-linked genes and lncRNAs, a total of 809 immune-related lncRNAs were collected. 77 differentially expressed immune-related lncRNAs were identified (logFC>2,FDR<0.01). The identified differentially-expressed immune-linked lncRNAs were used to develop differential immune-linked lncRNA pairs. Univariate and modified Lasso regression analysis identified 40 differentially expressed immune linked lncRNAs pairs, 17 of which were incorporated in the Cox proportional hazard model by a stepwise approach. The signature could well predict the survival of patients, and the area under the receiver operating characteristic (ROC) of 17 lncRNA pairs predicted 1, 3, and 5-year survival rates (AUC) were all greater than 0.74. Kaplan-Meier analysis found that patients at low risk had longer survival than those in the high-risk group (p<.001). In addition, T stage, survival status, N stage, and clinical stage, were remarkably linked to the risk. The high- and low risk groups were correlated with tumor invading immune cells like macrophages, CD8+ T-cells, monocytes, along with CD4+ T-cells. ICI-related biomarker correlation analysis showed high risk scores were positively linked to high CDK8 expression (p<0.001) and negatively correlated with BTLA , LAG3 and PDCD1 (p<0.001). High-risk scores were correlated with lower IC50 for chemotherapeutics like Docetaxel (p<0.01), indicating that this model can predict chemotherapeutic efficacy.ConclusionsOur results offer promising prospects for identifying innovative molecular targets of immunotherapy and to improve therapeutic approaches for head and neck squamous cell carcinoma patients.

scholarly journals How Long Non-Coding RNAs and MicroRNAs Mediate the Endogenous RNA Network of Head and Neck Squamous Cell Carcinoma: a Comprehensive Analysis

2018 ◽  
Vol 50 (1) ◽  
pp. 332-341 ◽  
Author(s):  
Guomiao Zhao ◽  
Yaru Fu ◽  
Zhifang Su ◽  
Rongling wu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Metastasis ◽  
Lung Squamous Cell Carcinoma ◽  
Neck Squamous Cell Carcinoma ◽  
Differentially Expressed ◽  
Clinical Prognosis ◽  
Non Coding Rnas

Background/Aims: Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to compete for microRNAs (miRNAs) in cancer metastasis. Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers and rare biomarkers could predict the clinical prognosis of this disease and its therapeutic effect. Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify differentially expressed mRNAs (DEmRNAs) that might be key genes. GO enrichment and protein–protein interaction (PPI) analyses were performed to identify the principal functions of the DEmRNAs. An lncRNA-miRNA-mRNA network was constructed to understand the regulatory mechanisms in HNSCC. The prognostic signatures of mRNAs, miRNAs, and lncRNAs were determined by Gene Expression Profiling Interactive Analysis (GEPIA) and using Kaplan–Meier survival curves for patients with lung squamous cell carcinoma. Results: We identified 2,023 DEmRNAs, 1,048 differentially expressed lncRNAs (DElncRNAs), and 82 differentially expressed miRNAs (DEmiRNAs). We found that eight DEmRNAs, 53 DElncRNAs, and 16 DEmiRNAs interacted in the ceRNA network. Three ceRNAs (HCG22, LINC00460 and STC2) were significantly correlated with survival. STC2 transcript levels were significantly higher in tumour tissues than in normal tissues, and the STC2 expression was slightly upregulated at different stages of HNSCC. Conclusion: LINC00460, HCG22 and STC2 exhibited aberrant levels of expression and may participate in the pathogenesis of HNSCC.

scholarly journals Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 286
Author(s):  
Yen Vo-Hoang ◽  
Sergio Paiva ◽  
Leilei He ◽  
Sébastien Estaran ◽  
Yong Teng
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Critical Role ◽  
In Vitro Cytotoxicity ◽  
Neck Squamous Cell Carcinoma ◽  
Protein Levels ◽  
Design And Synthesis

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related deaths and calls for new druggable targets. We have previously highlighted the critical role of ADP-ribosylation factor-1 (Arf1) activation in HNSCC. In the present study, we address the question whether targeting Arf1 could be proposed as a valuable strategy against HNSCC. Methods: We rationally designed and synthesized constrained ATC-based (4-amino-(methyl)-1,3-thiazole-5-carboxylic acid) γ-dipeptides to block Arf1 activation. We evaluated the effects of these γ-dipeptides in HNSCC cells: The cell viability was determined in 2D and 3D cell cultures after 72 h treatment and Arf1 protein levels and activity were assessed by GGA3 pull-down and Western blotting assays. Results: Targeting Arf1 offers a valuable strategy to counter HNSCC. Our new Arf1-targeting compounds revealed a strong in vitro cytotoxicity against HNSCC cells, through inhibiting Arf1 activation and its downstream pathways. Conclusions: Arf1-targeting γ-dipeptides developed in this study may represent a promising targeted therapeutic to improve managing the HNSCC disease.

scholarly journals Comprehensive review of genetic factors contributing to head and neck squamous cell carcinoma development in low-risk, nontraditional patients

Head & Neck ◽  
2018 ◽  
Vol 40 (5) ◽  
pp. 943-954 ◽  
Author(s):  
Morgan A. Gingerich ◽  
Joshua D. Smith ◽  
Nicole L. Michmerhuizen ◽  
Megan Ludwig ◽  
Samantha Devenport ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Genetic Factors ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Comprehensive Review

scholarly journals Development of an Immunogenomic Landscape-Based Prognostic Index of Head and Neck Squamous Cell Carcinoma

2020 ◽  
Vol 7 ◽  
Author(s):  
Jinhua Long ◽  
Shichao Zhang ◽  
Xianlin Zeng ◽  
Yan Ouyang ◽  
Yun Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Index ◽  
Neck Squamous Cell Carcinoma ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cox Analysis ◽  
Upregulated Genes

Head and neck squamous cell carcinoma (HNSCC) is the eighth leading cancer by incidence worldwide, with approximately 700,000 new cases in 2018 (accounting for 11% of all cancers). The occurrence and development of tumors are closely related to the immunological function of the body and sensitivity to treatment schemes as well as prognosis. It is urgent for clinicians to systematically study patients’ immune gene maps to help select a treatment plan and analyze the potential to cure HNSCC. Here, the transcriptomic data of HNSCC samples were downloaded from The Cancer Genome Atlas (TCGA), and 4,793 genes differentially expressed in normal and cancer tissues of HNSCC were identified, including 1,182 downregulated and 3,611 upregulated genes. From these genes, 400 differentially expressed immune-related genes (IRGs) were extracted, including 95 downregulated genes and 305 upregulated genes. The prognostic values of IRGs were evaluated by univariate Cox analysis, and 236 genes that were significantly related to the overall survival (OS) of patients were identified. The signaling pathways that play roles in the prognosis of IRGs were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the expression profiles of IRGs and OS in 499 HNSCC patients based on TCGA dataset were integrated. Potential molecular mechanisms and characteristics of these HNSCC-specific IRGs were further explored with the help of a new prognostic index based on IRGs developed by least absolute shrinkage and selection operator (LASSO) Cox analysis. A total of 64 hub genes (IRGs associated with prognosis) were markedly associated with the clinical outcome of HNSCC patients. KEGG functional enrichment analysis revealed that these genes were actively involved in several pathways, e.g., cytokine–cytokine receptor interaction, T-cell receptor signaling, and natural killer cell-mediated cytotoxicity. IRG-based prognostic signatures performed moderately in prognostic predictions. Interestingly, the prognostic index based on IRGs reflected infiltration by several types of immune cells. These data screened several IRGs of clinical significance and revealed drivers of the immune repertoire, demonstrating the importance of a personalized IRG-based immune signature in the recognition, surveillance, and prognosis of HNSCC.

scholarly journals Identification of Immune-related lncRNA Panel for Predicting Immune Checkpoint Blockade and Prognosis in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Chongchang Zhou ◽  
Guowen Zhan ◽  
Zhisen Shen ◽  
Yi Shen ◽  
Hongxia Deng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Risk Model ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Abstract Immunotherapy is changing head and neck squamous cell carcinoma (HNSCC) treatment pattern. According to the Chinese Society of Clinical Oncology (CSCO) guidelines, immunotherapy has been deemed as first-line recommendation for recurrent/metastatic HNSCC, marking that advanced HNSCC has officially entered the era of immunotherapy. Long non-coding RNAs impact every step of cancer immunity. Therefore, reliable immune-lncRNA able to accurately predict the immune landscape and survival of HNSCC are crucial to clinical management. In the current study, we downloaded the transcriptomic and clinical data of HNSCC from The Cancer Genome Altas and identified differentially expressed immune-related lncRNAs (DEir-lncRNAs). Further then, Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to identify proper DEir-lncRNAs to construct optimal risk model. Low-risk and high-risk groups were classified based on the optimal cut-off value generated by the areas under curve for receiver operating characteristic curves (AUC), and Kaplan-Meier survival curves were utilized to validate the prediction model. We then evaluated the model based on the clinical factors, immune cell infiltration, chemotherapeutic and immunotherapeutic efficacy between two groups. Our results constructed a risk model consisted of 18 DEir-lncRNA pairs showing significantly association with survival of patients with HNSCC. Besides, HNSCC patients with low risk score significantly enriched of CD8+ T cell, and corelated with high chemosensitivity and immunotherapeutic sensitivity. In summary, our risk model could be served as a promising clinical prediction indicator, effective discoursing of the immune cell infiltration of HNSCC patients, and distinguishing patients who could benefit from chemotherapy and immunotherapy.

scholarly journals A Ferroptosis-Related Gene Signature for Predicting the Prognosis and Drug Sensitivity of Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Lu ◽  
Yihua Wu ◽  
Shengyun Huang ◽  
Dongsheng Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Drug Sensitivity ◽  
Risk Group ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Survival Prediction ◽  
Prognostic Signature

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and has a high mortality. Ferroptosis, an iron-dependent form of programmed cell death, plays a crucial role in tumor suppression and chemotherapy resistance in cancer. However, the prognostic and clinical values of ferroptosis-related genes (FRGs) in HNSCC remain to be further explored. In the current study, we constructed a ferroptosis-related prognostic model based on the Cancer Genome Atlas database and then explored its prognostic and clinical values in HNSCC via a series of bioinformatics analyses. As a result, we built a four-gene prognostic signature, including FTH1, BNIP3, TRIB3, and SLC2A3. Survival analysis showed that the high-risk group presented significantly poorer overall survival than the low-risk group. Moreover, the ferroptosis-related signature was found to be an independent prognostic predictor with high accuracy in survival prediction for HNSCC. According to immunity analyses, we found that the low-risk group had higher anti-tumor immune infiltration cells and higher expression of immune checkpoint molecules and meanwhile corelated more closely with some anti-tumor immune functions. Meanwhile, all the above results were validated in the independent HSNCC cohort GSE65858. Besides, the signature was found to be remarkably correlated with sensitivity of common chemotherapy drugs for HNSCC patients and the expression levels of signature genes were also significantly associated with drug sensitivity to cancer cells. Overall, we built an effective ferroptosis-related prognostic signature, which could predict the prognosis and help clinicians to perform individualized treatment strategy for HNSCC patients.

scholarly journals Microarray Analysis of Serum mRNA in Patients with Head and Neck Squamous Cell Carcinoma at Whole-Genome Scale

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Markéta Čapková ◽  
Jana Šáchová ◽  
Hynek Strnad ◽  
Michal Kolář ◽  
Miluše Hroudová ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Microarray Analysis ◽  
Squamous Cell ◽  
Early Stage ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Neck Squamous Cell Carcinoma

With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey’sPvalue<0.05) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease.

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