scholarly journals Tumor microenvironment characterization and Immune infiltration in head and neck squamous cell carcinoma

2020 ◽  
Author(s):  
Zenghong Wu ◽  
Xun Niu ◽  
Xi-Yue Xiao ◽  
Xiong Chen
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Survival Function ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Infiltration ◽  
Significant Difference

Abstract Background : Head and neck squamous cell carcinoma (HNSCC), a basic malignant tumor of the head and neck distinct. As a famous heterogeneous disease, the jobs of immune cells inside the tumor-related as yet missing for HNSCC, particularly in current immunotherapy. Method: We explored the TME, TMB and evaluate the 22 TIICs subsets of immune response based on GEO and TCGA database of HNSCC to explore its relationship with atomic subpopulation, survival, function and expression difference and reveal potential targets and biomarkers for immunotherapy. Results: Observing the download of GSE6631 database contained 22 HNSCC samples and 22 normal samples and TCGA database contained 111 HNSCC and 12 normal tissues. The results suggested that the expression of macrophages M0 and T cells CD4 memory resting was significant difference and may plays an important role in regulate cancer progression ( P <0.05). The result of tumor mutational burden revealed that the most common somatic mutations variant classification was missense mutation, the most common DNA sequence polymorphism type was SNP, the most common single nucleotide variants (SNV) class was C>T, the variants per sample median was 78 in HNSCC patients. Top 10 mutated genes that related to TMB was TP53, TTN, FAT1, MUC16, CDKN2A, CSMD3, SYNE1, LRP1B, NOTCH1 and PIK3CA. We portrayed the immune scene in detail, uncovering the awesome immune infiltration styles of various subtypes in HNSCC. Conclusion: The intricate connection between TIIC, TMB and genomic alterations was additionally set up. Our paintings advance the information of immune response and offers significant assets for research to enhance immunotherapy.

scholarly journals Tumor microenvironment characterization and Immune infiltration in head and neck squamous cell carcinoma

2019 ◽  
Author(s):  
zenghong wu ◽  
xun niu ◽  
Xi-Yue Xiao ◽  
xiong chen
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Survival Function ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Infiltration ◽  
Significant Difference

Abstract Objection: Head and neck squamous cell carcinoma (HNSCC), a basic malignant tumor of the head and neck distinct. As a famous heterogeneous disease, the jobs of immune cells inside the tumor-related as yet missing for HNSCC, particularly in current immunotherapy. Method: We explored the TME, TMB and evaluate the 22 TIICs subsets of immune response based on GEO and TCGA database of HNSCC to explore its relationship with atomic subpopulation, survival, function and expression difference and reveal potential targets and biomarkers for immunotherapy. Results: Observing the download of GSE6631 database contained 22 HNSCC samples and 22 normal samples and TCGA database contained 111 HNSCC and 12 normal tissues. The results suggested that the expression of macrophages M0 and T cells CD4 memory resting was significant difference and may plays an important role in regulate cancer progression (P<0.05). The result of tumor mutational burden revealed that the most common somatic mutations variant classification was missense mutation, the most common DNA sequence polymorphism type was SNP, the most common single nucleotide variants (SNV) class was C>T, the variants per sample median was 78 in HNSCC patients. Top 10 mutated genes that related to TMB was TP53, TTN, FAT1, MUC16, CDKN2A, CSMD3, SYNE1, LRP1B, NOTCH1 and PIK3CA. We portrayed the immune scene in detail, uncovering the awesome immune infiltration styles of various subtypes in HNSCC. Conclusion: The intricate connection between TIIC, TMB and genomic alterations was additionally set up. Our paintings advance the information of immune response and offers significant assets for research to enhance immunotherapy.

scholarly journals Characterization of tumor microenvironment and Immune infiltration in head and neck squamous cell carcinoma

2020 ◽  
Author(s):  
zenghong wu ◽  
qing cheng
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Survival Function ◽  
Median Number ◽  
Neck Squamous Cell Carcinoma ◽  
Single Nucleotide Variants ◽  
Immune Infiltration ◽  
Set Up

Abstract Background: Head and neck squamous cell carcinoma (HNSCC), is a frequent malignant tumor of the head and neck. Most HNSCC arise in the lip, oral cavity, paranasal sinuses, oropharynx, larynx, nasopharynx, and the pharynx. HNSCC is a heterogeneous disease entity, and the role of immune cells in HNSCC, particularly in immunotherapy has not yet been extensively studied. Method: In this study, we applied CIBERSORT to infer the infiltration of 22 subsets of TIICs using gene expression data. This was to determine the relationship of the immune subpopulation, patients’ survival, function, and expression differences to reveal potential targets and biomarkers for immunotherapy. Results: Somatic mutations were the most common and the variant classification was missense mutation. The most common DNA sequence polymorphism type was SNP and the most common single nucleotide variants (SNV) class was C>T. The median number of variants per sample was 78 in HNSCC patients. The top 10 mutated genes related to TMB were TP53, TTN, FAT1, MUC16, CDKN2A, CSMD3, SYNE1, LRP1B, NOTCH1, and PIK3CA. We portrayed the immune scene in detail, uncovering the awesome immune infiltration styles of various subtypes in HNSCC. Conclusion: The intricate connection between TIIC, TMB, and genomic alterations was additionally set up. Our paintings advance the information of immune response and offer significant assets for research to enhance immunotherapy.

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 Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Tumor Tissues ◽  
Significant Difference

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.

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.

Efficacy and safety of systemic treatments for patients with recurrent/metastatic head and neck squamous cell carcinoma: A systematic review and network meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18001-e18001
Author(s):  
Lingbin Meng ◽  
Rui Ji ◽  
Huanhuan Wang ◽  
Xin Jiang
Keyword(s):  
Systematic Review ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Meta Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Efficacy And Safety ◽  
Treatment Regimens ◽  
Significant Difference

e18001 Background: A variety of systemic chemotherapy regimens have been used for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, most guidelines were derived from a single clinical trial, and no studies have comprehensively compared their efficacy and safety. This study is aimed to compare the efficacy and safety of systemic chemotherapies for patients with R/M HNSCC. Methods: We conducted a systematic review of published studies in PubMed, Embase, Web of Science, and Cochrane Library databases up to July 31, 2020. Studies were included if they were randomized controlled clinical trials including treatment regimens recommended by the latest NCCN guidelines. Eligible studies should report at least one of the following outcomes: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and ≥3 adverse events rate (AEs). Literature screening, data extraction and quality assessment were independently conducted by two researchers. Disputes were settled by a panel of other researchers. Network meta-analysis was used to compare the efficacy and safety of various treatment regimens. Heterogeneity and consistency using the Bayesian model were evaluated in the network meta-analysis. Results: Eighteen eligible trials involving 4930 patients and 15 treatment regimens were included. Cetuximab/platinum/5-FU regimen showed higher ORR values than the following agents, including cisplatin/5-FU (odds ratio 2.96, 95% credible interval 1.42 to 6.15), cisplatin (5.43, 1.90-15.54), 5-FU (8.12, 2.22-29.61), methotrexate (8.25, 2.86-23.79), cetuximab (10.16, 1.44-71.48), and afatinib (3.64, 1.00-13.32). Immunotherapy regimens pembrolizumab/platinum/5-FU and pembrolizumab alone also showed significantly higher ORR values than these agents, while nivolumab alone showed higher ORR than the single agents. However, no significant difference was observed between Cetuximab/platinum/5-FU and pembrolizumab/platinum/5-FU. Regarding ≥3 AEs, cisplatin/paclitaxel caused the highest toxicity. No significant difference was observed on OS and PFS among all these treatment regimens. Conclusions: Cetuximab/platinum/5-FU, pembrolizumab/platinum/5-FU or pembrolizumab alone displayed high ORR with low AE rate. Nivolumab also showed better efficacy than other single agents. Although it was reported that pembrolizumab/platinum/5-FU showed better efficacy than cetuximab/platinum/5-FU, we did not find a statistically significant improvement in ORR, OS or PFS when comparing the two regimens. Therefore, further prospective trials comparing these treatment regimens remain warranted.

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