scholarly journals Autophagy-Related Signature for Head and Neck Squamous Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Cheng Li ◽  
Zeng-hong Wu ◽  
Kun Yuan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Risk Group ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Kaplan Meier

Background. Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in the world, with low survival and poor quality of life. Autophagy-associated genes (ATGs) have been reported to be involved in the initiation and progression of malignancies. Here, we aimed to investigate the association between autophagy-associated genes and the outcomes in HNSCC patients. Methods. We obtained ATGs with prognostic values by analyzing the datasets from The Cancer Genome Atlas (TCGA) and Human Autophagy Database (HADb). The enrichment functions of autophagy differential genes were analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The Kaplan-Meier method was applied to the survival curve analysis. A prognostic autophagy-related gene signature was established, and its independence was verified. Results. We acquired a total of 529 samples and 232 ATGs; further, we identified 45 genes associated with prognosis and built a prognosis autophagy signature based on risk score of 15 genes. Patients were divided into two groups based on risk scores. The Kaplan-Meier curve illustrated that the survival rate of the high-risk group was significantly lower than that of the low-risk group in both the training group and validation group. The ROC curve revealed that the risk score had the highest AUC value in the 3rd and 5th years, reaching 0.703 and 0.724, which are higher than other risk factors such as gender, age, and TNM stage. The nomogram further confirmed its weight in the prognosis of HNSCC patients. Through KEGG and GO enrichment analyses, we observed that ATGs were involved in the tumorigenesis and invasion of tumor by various mediating pathways. We gained 3 hub genes (MAP1LC3B, FADD, and LAMP1) and further analyzed the survival curves, mutations, differential expressions, and their roles in tumors on the online websites. Conclusion. We identified a novel autophagy-related signature that may provide promising biomarker genes for the treatment and prognosis of HNSCC. We need to validate its prognostic value by applying it to the clinic.

scholarly journals A Novel Ferroptosis-Related Gene Signature to Predict Prognosis in Patients with Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Li Xu ◽  
Ying-ying Li ◽  
Yang-chun Zhang ◽  
Yong-xu Wu ◽  
Dan-dan Guo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Tnm Staging ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis

The clinical TNM staging system is currently used to evaluate the prognosis of head and neck squamous cell carcinoma (HNSCC). The 5-year survival rate for patients with HNSCC is less than 50%, which is attributed to the lack of reliable prognostic biomarkers. Ferroptosis-related genes (FRGs) regulate cancer initiation and progression. Therefore, we analyzed the correlation between FRGs and the clinical outcomes of patients with HNSCC. A typical prognostic model of FRGs for HNSCC was constructed using bioinformatics tools and data from public databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and GeneCards. The model was generated based on the following six FRGs: ATG5, PRDX6, OTUB1, FTH1, SOCS1, and MAP3K5. The accuracy of model prediction was analyzed systematically. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. The AUC for 1-year, 3-year, and 5-year survival were 0.645, 0.721, and 0.737, respectively, in the training set (TCGA cohort) and 0.726, 0.620, and 0.584, respectively, in the validation set (GSE65858). The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that six FRGs were enriched in the ferroptosis pathway. A novel FRG prognostic signature model was established for HNSCC. The findings of this study reveal that FRGs are potential biomarkers for HNSCC.

scholarly journals JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Jing ◽  
Dandan Liu ◽  
Qingchuan Lai ◽  
Linqi Li ◽  
Mengqian Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
In Vivo Experiments

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

scholarly journals A TP53 mutation model for the prediction of prognosis and therapeutic responses in head and neck squamous cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Congyu Shi ◽  
Shan Liu ◽  
Xudong Tian ◽  
Xiaoyi Wang ◽  
Pan Gao
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Risk Group ◽  
High Risk Group ◽  
Mutation Model ◽  
Therapeutic Responses

Abstract Background Tumor protein p53 (TP53) is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSC), and TP53 mutations are associated with inhibited immune signatures and poor prognosis. We established a TP53 mutation associated risk score model to evaluate the prognosis and therapeutic responses of patients with HNSC. Methods Differentially expressed genes between patients with and without TP53 mutations were determined by using data from the HNSC cohort in The Cancer Genome Atlas database. Patients with HNSC were divided into high- and low-risk groups based on a prognostic risk score that was generated from ten TP53 mutation associated genes via the multivariate Cox regression model. Results TP53 was the most common mutant gene in HNSC, and TP53 mutations were associated with immunogenic signatures, including the infiltration of immune cells and expression of immune-associated genes. Patients in the high-risk group had significantly poorer overall survival than those in the low-risk group. The high-risk group showed less response to anti-programmed cell death protein 1 (PD-1) therapy but high sensitivity to some chemotherapies. Conclusion The risk score based on our TP53 mutation model was associated with poorer survival and could act as a specific predictor for assessing prognosis and therapeutic response in patients with HNSC.

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
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.

scholarly journals AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 347 ◽  
Author(s):  
Xiaolian Gu ◽  
Lixiao Wang ◽  
Linda Boldrup ◽  
Philip Coates ◽  
Robin Fahraeus ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Positive Impact ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Enhancer Rna ◽  
Kaplan Meier ◽  
Significant Survival

A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan–Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the “immune system process” being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.

scholarly journals Clinical Significance of the Interleukin 24 mRNA Level in Head and Neck Squamous Cell Carcinoma and Its Subgroups: An In Silico Investigation

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Lan-Lan Qiu ◽  
Xiao-Guohui Zhang ◽  
Gang Chen ◽  
Yi-Wu Dang ◽  
Zhi-Guang Huang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Mrna Level ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Summary Receiver Operating Characteristic ◽  
Standard Mean Difference ◽  
Potential Marker

IL24 mRNA is known to have an apoptotic effect on cancer cells but not on noncancer cells. However, the expression level of the IL24 mRNA in head and neck squamous cell carcinoma (HNSCC) and its subgroups is rarely studied. In this study, the clinical implication of IL24 mRNA was evaluated in the common subgroups of HNSCC, including oral squamous cell carcinoma (OSCC), nasopharyngeal carcinoma (NPC), and laryngeal squamous cell carcinoma (LSCC) for analysis. Substantial IL24 mRNA expression data were calculated from several databases, such as the Gene Expression Omnibus (GEO), ArrayExpress, Sequence Read Archive (SRA), ONCOMINE, and The Cancer Genome Atlas (TCGA) databases. We ultimately collected a total of 41 microarrays and RNA-seq including 1,564 HNSCC and 603 noncancer tissue samples. IL24 mRNA was highly expressed in OSCC, LSCC, and NPC as shown by the separated standard mean difference (SMD), as well as HNSCC as a whole part (SMD = 1.47, 95% confdence interval (CI) = 1.24−1.70, P<0.0001). In all subgroups, the IL24 mRNA upregulation had the ability to distinguish cancer from noncancer tissue with area under the curves (AUCs) of the summary receiver operating characteristic (sROC) higher than 0.85. In conclusion, IL24 mRNA may be used as a potential marker for cancer screening, and its clinical diagnostic value needs to be further studied. It also provides a new idea for the treatment of the IL24 gene in HNSCC and its subgroups in the future.

scholarly journals Seven LncRNA-mRNA based risk score predicts the survival of head and neck squamous cell carcinoma

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhi-Li Zhang ◽  
Li-jing Zhao ◽  
Liang Chai ◽  
Shui-Hong Zhou ◽  
Feng Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma

scholarly journals Gene Model Related to m6A Predicts the Prognostic Effect of Immune Infiltration on Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yaping Deng ◽  
Kehua Li ◽  
Fengwu Tan ◽  
Hanbo Liu
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Microenvironment

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive solid tumor. Because most studies have focused on the intrinsic carcinogenic pathways of tumors, we focused on the relationship between N6-methyladenosine (m6A) and the prognosis of HNSCC in the tumor immune microenvironment. We downloaded RNA-seq data from the TCGA dataset and used univariate Cox regression to screen m6A-related lncRNAs. The expression value of LASSO-screened genes was the sum of LASSO regression coefficients. We then evaluated relationships between the risk score and cellular components or cellular immune response. Differences in immune response under various algorithms were visualized with heat maps. The GSVA package in R was used to analyze GO, BP, KEGG, and hallmark gene sets of immune checkpoint clusters and immune checkpoint scores. The GSEA analysis was performed with the cluster profile package, yielding 21 m6A genes. Related lncRNAs were screened with Pearson’s correlations, and the resulting 442 lncRNAs were screened using single-factor analysis. Eight lncRNAs closely related to prognosis were identified through survival random forest. Survival analysis showed that patients with a high risk score had a poor prognosis. Low- and high-risk-score groups differed significantly in m6A gene expression. Prognostic scores from different algorithms were significantly correlated with B cells, T cells, and memory cells in the immune microenvironment. Expression of immune checkpoints and signal pathways differed significantly across risk-score groups, suggesting that m6A could mediate lncRNA-induced immune system dysfunction and affect HNSCC development. A comprehensive study of tumor-cell immune characteristics should provide more insight into the complex immune microenvironment, thus contributing to the development of new immunotherapeutic agents.

scholarly journals Bioinformatics analysis of the expression and role of microRNA-221-3p in the head and neck squamous cell carcinoma

2020 ◽  
Author(s):  
Ziyan Zhou ◽  
Wu Wenling ◽  
Li Jixi ◽  
Liu Chang ◽  
Xiao Zixi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Target Genes ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
High Rate ◽  
Summary Receiver Operating Characteristic

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer subtype globally, associated with a high rate of morbidity and mortality. However, the target genes of miR-221-3p and the underlying mechanism involved in HNSCC were not known. Therefore, in the current study, we studied the role of miR-221-3p in the HNSCC. Methods Tissues collected from 48 control and 21 HNSCC patients were processed to check the differential expression of miR-221-3p by Real-time RT-Polymerase Chain Reaction (RT-qPCR). Overexpression of microRNA-221-3p (miR-221-3p) is significantly correlated to the onset and progression of HNSCC. We also conducted the meta-analysis of the cancer literature from the cancer genome atlas (TCGA) and the Gene Expression Omnibus (GEO) database to estimate the expression of miR-221-3p in HNSCC. The miR-221-3p target genes in the HNSCC were predicted with the miRWalk and TCGA databases, and functionally annotated via the Gene Ontology Finally, Spearman’s analysis was used to determine the role of the related target genes in important pathways involved in the development of HNSCC. Results We observed a significantly higher expression of miR-221-3p in HNSCC compared to the normal with a summary receiver operating characteristic (sROC) of 0.86(95% Cl: 0.83,0.89). The KEGG and GO comprehensive analysis predicted that miR-221-3p might be involved in the development of HNSCC through the following metabolic pathways, viz Drug metabolism - cytochrome P450 UGT1A7 and MAOB may be important genes for the role of mir-221-3p. Conclusions Our results indicate that miR-221-3p may be used as a non-invasive and hypersensitive biomarker in the diagnosis. Thus, it can be concluded that miR-221-3p is an extremely important gene locus involved in the process of the deterioration and eventual tumorigenesis of HNSCC.

scholarly journals A Novel Glycolysis-related Gene Signature for Survival Prediction in Patients with Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Haimei Qin ◽  
Junli Wang ◽  
Biyun Liao ◽  
Zhonglin Liu ◽  
Rong Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Risk Group ◽  
Gene Signature ◽  
Neck Squamous Cell Carcinoma ◽  
Related Gene ◽  
Cancer Subtypes

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is most diagnosed at an advanced stage with poor prognosis. Single gene biomarkers cannot have enough predictive ability in HNSCC. Glycolysis participating in cancers was verified. Thus, this study aimed to identify glycolysis-related gene signature predict the outcome of HNSCC. Methods: The mRNA expression data of HNSCC downloaded The Cancer Genome Atlas (TCGA) project was analyzed by Gene Set Enrichment Analysis (GSEA). We use the Cox proportional regression model to construct a prognostic model. Kaplan–Meier and receiver operating characteristic (ROC) curves were employed to estimate the signature. We also analyzed the relationship of the signature and cancer subtypes. Results: We identified nine glycolysis-related genes including G6PD, EGFR, ALDH2, GPR87, STC2, PDK3, ELF3, STC1 and GNPDA1 as prognosis-related genes signature in HNSCC. HNSCC patients were divided into high and low risk group according to the signature. High risk group showed more poor prognosis and the risk score can precisely predict the prognosis of HNSCC. Additionally, the signature also can be used in cancer subtypes. Conclusion: This study established the 9-mRNA glycolysis signature which may serve as a prospective biomarker for prognosis and novel treatment target in HNSCC.

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