scholarly journals Identification of a Costimulatory Molecule Gene Signature to Predict Survival and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Ling Aye ◽  
Xiaole Song ◽  
Jingyi Yang ◽  
Li Hu ◽  
Xicai Sun ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Risk Factor ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Costimulatory Molecule ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide. Checkpoint blockade immunotherapy has made tremendous progress in the treatment of a variety of cancers in recent years. Costimulatory molecules constitute the foundation of cancer immunotherapies and are deemed to be promising targets for cancer treatment. This study attempted to evaluate the potential value of costimulatory molecule genes (CMGs) in HNSCC.Materials and MethodsBased on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, we identified the prognostic value of CMGs in HNSCC. Subsequently, CMGs-based signature (CMS) to predict overall survival of HNSCC patients was established and validated. The differences of downstream pathways, clinical outcomes, immune cell infiltration, and predictive immunotherapy responses between different CMS subgroups were investigated via bioinformatic algorithms. We also explored the biological functions of TNFRSF12A, one risk factor of CMS, by in vitro experiments.ResultsAmong CMGs, 22 genes were related to prognosis based on clinical survival time in HNSCC. Nine prognosis-related CMGs were selected to establish CMS. CMS was an independent risk factor and could indicate the survival of HNSCC patients, the component of tumor-infiltrating lymphocytes, and the immunotherapy response rate. Functional enrichment analysis confirmed that CMS might involve immune-relevant processes. Additionally, TNFRSF12A was related to poor prognosis and enhanced malignant phenotype of HNSCC.ConclusionCollectively, CMS could accurately indicate prognosis, evaluate the tumor immune microenvironment, and predict possible immunotherapy outcomes for 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 Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jili Cui ◽  
Lian Zheng ◽  
Yuanyuan Zhang ◽  
Miaomiao Xue
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Hub Genes ◽  
Significant Difference ◽  
Dnmt1 Expression

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.

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 Highly Multiplexed Digital Spatial Profiling of the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Arutha Kulasinghe ◽  
Touraj Taheri ◽  
Ken O’Byrne ◽  
Brett G. M. Hughes ◽  
Liz Kenny ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Neck Squamous Cell Carcinoma ◽  
Protein Markers ◽  
Spatial Profiling

BackgroundImmune checkpoint inhibitors (ICI) have shown durable and long-term benefits in a subset of head and neck squamous cell carcinoma (HNSCC) patients. To identify patient-responders from non-responders, biomarkers are needed which are predictive of outcome to ICI therapy. Cues in the tumor microenvironment (TME) have been informative in understanding the tumor-immune contexture.MethodsIn this preliminary study, the NanoString GeoMx™ Digital Spatial Profiling (DSP) technology was used to determine the immune marker and compartment specific measurements in a cohort of HNSCC tumors from patients receiving ICI therapy.ResultsOur data revealed that markers involved with immune cell infiltration (CD8 T-cells) were not predictive of outcome to ICI therapy. Rather, a number of immune cell types and protein markers (CD4, CD68, CD45, CD44, CD66b) were found to correlate with progressive disease. Cross platform comparison with the Opal Vectra (Perkin Elmer) for a number of markers across similar regions of interest demonstrated concordance for pan-cytokeratin, CD8, and PD-L1.ConclusionThis study, to our knowledge, represents the first digital spatial analysis of HNSCC tumors. A larger cohort of HNSCC will be required to orthogonally validate the findings.

scholarly journals Characterization of the immune cell infiltration landscape in head and neck squamous cell carcinoma to aid immunotherapy

2020 ◽  
Author(s):  
Xinhai Zhang ◽  
Tielou Chen ◽  
Boxin Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Stromal Component

Abstract Background: The tumor microenvironment chiefly consists of tumor cells, and tumor-infiltrating immune cells admixed with the stromal component. The recent clinical trial has shown that the tumor immune cell infiltration is correlated with the sensitivity to immunotherapy and the prognosis of head and neck squamous cell carcinoma (HNSC). However, to date, the immune infiltrative landscape of HNSC has not yet been elucidated. Methods: We proposed two computational algorithms to unravel the immune infiltration landscape of 1029 HNSC patients. The Boruta algorithm and principal component algorithms (PCA) were employed to quantify three immune cell infiltration gene subtypes categorized as per the immune cell infiltrations pattern. Results: The high ICI score subtype was characterized by a higher tumor mutation burden (TMB) and the immune-activated signaling pathway. However, a low ICI score subtype was categorized as per the activation of immunosuppressive signaling pathways such as TGF-BETA, WNT signaling pathway, and lower TMB. Two immunotherapy cohorts confirmed patients with higher ICI score demonstrated significant therapeutic advantages and clinical benefits.Conclusions: This demonstrated that the ICI score could serve as an effective prognostic biomarker and predictive indicator for immunotherapy. A comprehensive understanding of the HNSC immune landscape might help in tailoring immunotherapeutic strategies for different patients.

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 Influence of Immune Microenvironment on Diagnosis and Prognosis of Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Guohong Liu ◽  
Chunjue Yuan ◽  
Jiaojiao Ma ◽  
Yunbao Pan ◽  
Haibo Xu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cells ◽  
Relative Proportion ◽  
Neck Squamous Cell Carcinoma ◽  
Functional Enrichment ◽  
Survival Prediction ◽  
Immune Microenvironment

Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy accompanied by noted alterations in various immune cells and cytokines. Recognition of the immune system’s role in contributing to cancer development is an important advancement in our original understanding of carcinoma. We obtained HNSCC gene expression and clinical data from The Cancer Genome Atlas (TCGA) database. We assessed the relative proportion of 22 Infiltrating immune cell types in both HNSCC and adjacent non-cancer tissues using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method, identifying the influence of the immune cells content in tumor staging and survival prediction. We further predicted the tumor purity, and the presence of infiltrating stromal/immune cells in HNSCC tissues using Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm, identifying its potential correlation with patient survival. Stromal and immune score-associated differentially expressed genes (DEGs) were subsequently verified and their roles in immune response were displayed by functional enrichment analysis and protein-protein interaction (PPI) network. Our research demonstrated the underlying association between the immune microenvironment and HNSCC, and the results were intended to serve as valuable terms for HNSCC diagnosis, prognosis, and targeted immune therapy.

Sign in / Sign up

Export Citation Format

Share Document