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 ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Data Resource

Abstract Recent researches have established that lncRNAs (long non-coding RNAs) could be exploited as new signatures for head and neck squamous cell carcinoma (HNSCC) diagnosis, prognosis, and treatment. Herein, HNSCC transcriptome data was abstracted from the Cancer Genome Atlas (TCGA) data resource, and uncovered immune linked lncRNAs 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. Overall, we identified 40 differentially expressed immune-linked lncRNA pairs, 17 of which were incorporated in the Cox regression model. Using this model, we can more effectively stratify patients based on poor survival results, positive clinicopathological features, specific tumor immune invasion status, low chemotherapy responsivity, and high expression of immunosuppressive biomarkers. Our data illustrated that the immune-linked lncRNA pairs signature have clinical prediction value for HNSCC.

scholarly journals Data Mining Identifies Six Proteins that Can Act as Prognostic Markers for Head and Neck Squamous Cell Carcinoma

2020 ◽  
Vol 29 ◽  
pp. 096368972092930
Author(s):  
Zeng-hong Wu ◽  
Yun-Tang ◽  
Qing Cheng
Keyword(s):  
Squamous Cell Carcinoma ◽  
Regression Analysis ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
High Throughput Sequencing ◽  
Cox Regression ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis

Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of the upper aerodigestive tract affecting the oral cavity, lips, paranasal sinuses, larynx, and nasopharynx. Proteogenomics combines proteomics and genomics and employs mass spectrometry and high-throughput sequencing technologies to identify novel peptides. The aim of this study was to identify potential protein biomarkers for clinical treatment of HNSCC. To achieve this, we utilized two sets of data, one on proteins from The Cancer Proteome Atlas (TCPA) and the other on gene expression from The Cancer Genome Atlas (TCGA) database, to evaluate dysfunctional proteogenomics microenvironment. Univariate Cox regression analysis was performed to examine the relationship between protein signatures and prognosis. A total of 19 proteins were significantly associated with overall survival (OS) of patients, of which E2F transcription factor 1 (E2F1; HR = 4.557, 95% CI = 1.810 to 11.469) and enhancer of zeste homolog 2 (EZH2; HR = 0.430, 95% CI = 0.187 to 0.984) were the most differentially expressed between patients with longer and shorter OS, respectively. Furthermore, multivariate Cox regression analysis on six proteins (ERALPHA, HER3, BRAF, P27, RAPTOR, and E2F1) was performed to build the prognostic model. The receiver operating characteristic curves were used to determine whether the expression pattern of survival-related proteins could provide an early prediction of the occurrence of HNSCC. Herein, we found an AUC of 0.720. Based on an online database, we identified novel protein markers for the prognosis of HNSCC. The findings of the present study may provide new insights into the development of new and reliable tools for precise cancer intervention.

scholarly journals A 8-gene-methylation-based Signature for Head and Neck Squamous Cell Carcinoma Prognosis

2021 ◽  
Author(s):  
Zihui Wang ◽  
Jingrun Yang ◽  
Lihong Liu
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cox Regression ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Gene Methylation ◽  
Cox Regression Analysis

Abstract Background Head and neck squamous cell carcinoma (HNSCC), accounting for 6% of systemic malignant tumors, has an increasing incidence rate year by year worldwide. A large number of studies have investigated the tumor markers to determine clinical stage, prognosis, treatment evaluation, predict relapses, and overall survival of HNSCC patients, with controversial results. Methods In this paper, we comprehensively analyzed gene expression and DNA methylation data sets of HNSCC and adjacent non-tumor samples from The Cancer Genome Atlas (TCGA). Univariate cox regression analysis followed by sure independence screening (SIS) were used for identifying differential methylation signatures to stratify patients with significantly different prognosis. Results We identified methylation levels of HS3ST1，TOMM34，RPL26L1，MTHFD2，ORC1，MYOSLID，UHRF1 and AL357033.3 as potential HNSCC prognosis signatures, and verified the correlation between their gene expression and the corresponding methylation. Their reliability for predicting the prognosis of HNSCC was confirmed in an independent dataset. Conclusions In conclusion, we built a 8-gene-methylation-based signature which can well assess the prognosis of HNSCC patients.

scholarly journals The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 689
Author(s):  
Li Cui ◽  
Huan Chen ◽  
Xinyuan Zhao
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Metabolic Enzyme ◽  
Cox Regression Analysis

Metabolic dysregulation has emerged as a crucial determinant of the clinical responses to immunotherapy. The aim of this study was to determine the clinical significance of the candidate immune-related metabolic enzymes (IRMEs) methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 (MTHFD2) in head and neck squamous cell carcinoma (HNSCC). The gene expression profile of HNSCC cohort and the corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed IRMEs were identified, and then, the prognosis-associated IRMEs were revealed by univariate cox regression analysis. The prognostic significance of MTHFD2 in HNSCC as well as the association between MTHFD2 and immune cell infiltration were further analyzed. A total of 121 significantly altered IRMEs were identified between HNSCC and normal tissues, and 21 IRMEs were found to be strongly associated with overall survival of HNSCC. Upregulation of MTHFD2 was positively correlated with adverse clinicopathological factors in TCGA HNSCC cohort, which was further validated with our own cohort using immunohistochemical analysis. Interestingly, bioinformatic analysis further revealed that increased MTHFD2 expression was negatively associated with NK cells activation, while positively correlated with mast cells activation. In conclusion, MTHFD2 overexpression is closely correlated with unfavorable prognosis of HNSCC, and it might play an important role in modulating the tumor immune microenvironment.

Significance of TP53 mutation in treatment and prognosis in head and neck squamous cell carcinoma

2021 ◽  
Vol 15 (1) ◽  
pp. 15-28
Author(s):  
Yu Jin ◽  
Xing Qin
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Tp53 Mutation ◽  
Cox Regression ◽  
Cancer Genome ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis

Background: TP53 is ranked as the most common mutated gene in head and neck squamous cell carcinoma (HNSCC). Results: The status of TP53 mutation was investigated on International Cancer Genome Consortium and The Cancer Genome Atlas database and TP53-related differentially expressed genes were screened out from transcriptome data and mutation information. A TP53-related prognostic gene signature ( TIMP4, ONECUT2, CGNL1, DMRTA2 and NKX2.3) was constructed based on Cox regression analysis and LASSO algorithm. Univariate and multivariate analyses were carried out to identify promising prognosticators for HNSCC. Conclusion: Our findings provide a well-rounded landscape of TP53 mutation in HNSCC and pave the groundwork for developing innovative and effective cancer treatment methods for HNSCC.

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 Identification of Three Autophagy-Related Long Non-Coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature

2021 ◽  
Vol 10 ◽  
Author(s):  
Ya Guo ◽  
Peng Tao Yang ◽  
Zhong Wei Wang ◽  
Kun Xu ◽  
Wei Hua Kou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Cox Regression ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Non Coding Rnas

Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Considerable evidence indicates that autophagy and non-coding RNA play essential roles in the biological processes involved in cancers, but associations between autophagy-related long non-coding RNAs (lncRNAs) and HNSCC remain unclear. In the present study, HNSCC RNA sequences and autophagy-related gene data were extracted from The Cancer Genome Atlas database and the Human Autophagy Database. A total of 1,153 autophagy-related lncRNAs were selected via calculating Pearson’s correlation coefficient. Three prognosis-related autophagy lncRNAs were identified via univariate Cox regression, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis. We also constructed a prognostic model based on these autophagy-related lncRNAs and evaluated its ability to accurately and independently predict the prognosis of HNSCC patients. The area under the curve (AUC) was 0.864 (3-year) and 0.836 (5-year), and our model can independently predict the prognosis of HNSCC. The prognostic value of the three autophagy lncRNAs was confirmed via analysis of samples from five databases. To further identify the functions of the three lncRNAs, a co-expression network was constructed and pathway analysis was performed. In that analysis the lncRNAs were correlated with 189 related genes and 20 autophagy-related genes, and these lncRNAs mainly involved homologous recombination, the Fanconi anemia pathway, the autophagy-related pathway, and immune-related pathways. In addition, we validated the expression levels of three lncRNAs and autophagy markers (ATG12, BECN1, and MAP1LC3B) based on TIMER, Oncomine, and HPA database analysis. Our results indicated that TTTY15 was increased in HPV positive and HPV negative HNSCC patients, and three autophagy markers were up-regulated in all HNSCCC patients. Lastly, association between three lncRNAs and autophagy markers was performed, and our results showed that TTTY15 and MIF-AS1 were associated with autophagy markers. Collectively, these results suggested that three autophagy-related lncRNAs have prognostic value in HNSCC patients.

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 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 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 Synthetic Evaluation of MicroRNA-1-3p Expression in Head and Neck Squamous Cell Carcinoma Based on Microarray Chips and MicroRNA Sequencing

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Yubing Chen ◽  
Mingjiang Liu ◽  
Hu Jin ◽  
Bo Peng ◽  
Luo Dai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Regulatory Pathways

Background. MicroRNA-1-3p (miR-1-3p) exerts significant regulation in various tumor cells, but its molecular mechanisms in head and neck squamous cell carcinoma (HNSCC) are still ill defined. This study is aimed at detecting the expression of miR-1-3p in HNSCC and at determining its significant regulatory pathways. Methods. Data were obtained from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Oncomine, ArrayExpress, Sequence Read Archive (SRA) databases, and additional literature. Expression values of miR-1-3p in HNSCC were analyzed comprehensively. The R language software was employed to screen differentially expressed genes, and bioinformatics assessment was performed. One sequence dataset (HNSCC: n = 484 ; noncancer: n = 44 ) and 18 chip datasets (HNSCC: n = 656 ; noncancer: n = 199 ) were obtained. Results. The expression of miR-1-3p in HNSCC was visibly decreased in compare with noncancerous tissues. There were distinct differences in tumor state ( P = 0.0417 ), pathological stage ( P = 0.0058 ), and T stage ( P = 0.0044 ). Comprehensive analysis of sequence and chip data also indicated that miR-1-3p was lowly expressed in HNSCC. The diagnostic performance of miR-1-3p in HNSCC is reflected in the sensitivity and specificity of the collection, etc. Bioinformatics analysis showed the possible biological process, cellular component, molecular function, and KEGG pathways of miR-1-3p in HNSCC. And ITGB4 was a possible target of miR-1-3p.Conclusions. miR-1-3p’s low expression may facilitate tumorigenesis and evolution in HNSCC through signaling pathways. ITGB4 may be a key gene in targeting pathways but still needs verification through in vitro experiments.

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