scholarly journals DOCK8 Serves as a Prognostic Biomarker and Is Related to Immune Infiltration in Patients With HPV Positive Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 28 ◽  
pp. 107327482110119
Author(s):  
Zeying Zhang ◽  
Yandong Bao ◽  
Lu Zhou ◽  
Yanling Ye ◽  
Weineng Fu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Biological Processes ◽  
Immune Infiltration ◽  
Favorable Prognosis

Purpose: Dedicator of cytokinesis 8 (DOCK8) was reported to have a vital link to immunoregulation. However, the mechanisms by which it drives immune infiltration in cancer remain uncertain. We tried to assess the role of DOCK8 in patients with cancer, especially human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC). Methods: Data on the expression and survival of DOCK8 in patients with various cancers were analyzed using the Oncomine and TIMER databases. The TIMER database assessed the relationship of DOCK8 with immune infiltration levels and various markers of multiple immune cells. Gene set enrichment analysis revealed tumor-associated biological processes related to DOCK8. ENCODE database was used to explore relevant transcription factors of DOCK8, and a PPI network was constructed using GENEMINIA. The expression and survival role of DOCK8 was confirmed in patients from independent GEO datasets. Results: We determined that DOCK8 expression was upregulated or downregulated in various cancers unlike in healthy tissues. A high expression of DOCK8 was significantly correlated with a favorable prognosis in HPV-positive HNSCC and lung adenocarcinoma (LUAD). Furthermore, multivariate Cox regression analysis revealed that DOCK8 was an independent prognostic factor of HPV-positive HNSCC. Additionally, elevated DOCK8 expression was positively correlated with multiple immune cell infiltration levels and immune marker expression associated with particular immune cell subsets. Also, 14 pathways involved in immune activities and carcinogenesis, 22 potential TFs, and co-expression proteins of DOCK8 indicated DOCK8 to be related to tumor-associated biological processes. Ultimately, we verified that DOCK8 is upregulated and confers a favorable overall survival and progression-free survival status in patients with HPV-positive HNSCC. Conclusion: These results elucidate that high expression of DOCK8 indicates a favorable prognosis in patients with HPV-positive HNSCC as well as increased microenvironmental immune infiltration levels. It would provide new insights into the prognosis predicting and clinical regimen decision making in patients with HPV-positive HNSCC.

scholarly journals Comprehensive Analysis of Myeloid Signature Genes in Head and Neck Squamous Cell Carcinoma to Predict the Prognosis and Immune Infiltration

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhifeng Liu ◽  
Diekuo Zhang ◽  
Chao Liu ◽  
Guo Li ◽  
Huihong Chen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Risk Model ◽  
Immune Therapy ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Infiltration ◽  
Signature Genes

Myeloid cells are a major heterogeneous cell population in the tumor immune microenvironment (TIME). Imbalance of myeloid response remains a major obstacle to a favorable prognosis and successful immune therapy. Therefore, we aimed to construct a risk model to evaluate the myeloid contexture, which may facilitate the prediction of prognosis and immune infiltration in patients with head and neck squamous cell carcinoma (HNSCC). In our study, six myeloid signature genes (including CCL13, CCR7, CD276, IL1B, LYVE1 and VEGFC) analyzed from 52 differentially expressed myeloid signature genes were finally pooled to establish a prognostic risk model, termed as myeloid gene score (MGS) in a training cohort and validated in a test cohort and an independent external cohort. Furthermore, based on the MGS subgroups, we were able to effectively identify patients with a poor prognosis, aggressive clinical parameters, immune cell infiltration status and immunotherapy response. Thus, MGS may serve as an effective prognostic signature and predictive indicator for immunotherapy response in patients with HNSCC.

scholarly journals The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4737
Author(s):  
Oliwia Koteluk ◽  
Antonina Bielicka ◽  
Żaneta Lemańska ◽  
Kacper Jóźwiak ◽  
Weronika Klawiter ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Patient Survival ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Expression Levels

Background: Transmembrane proteins (TMEM) constitute a large family of proteins spanning the entirety of the lipid bilayer. However, there is still a lack of knowledge about their function or mechanism of action. In this study, we analyzed the expression of selected TMEM genes in patients with head and neck squamous cell carcinoma (HNSCC) to learn their role in tumor formation and metastasis. Materials and Methods: Using TCGA data, we analyzed the expression levels of different TMEMs in both normal and tumor samples and compared those two groups depending on clinical-pathological parameters. We selected four TMEMs whose expression was highly correlated with patient survival status and subjected them to further analysis. The pathway analysis using REACTOME and the gene set enrichment analysis (GSEA) were performed to evaluate the association of those TMEMs with genes involved in hallmarks of cancer as well as in oncogenic and immune-related pathways. In addition, the fractions of different immune cell subpopulations depending on TMEM expression were estimated in analyzed patients. The results for selected TMEMs were validated using GEO data. All analyses were performed using the R package, Statistica, and Graphpad Prism. Results: We demonstrated that 73% of the analyzed TMEMs were dysregulated in HNSCC and depended on tumor localization, smoking, alcohol consumption, or HPV infection. The expression levels of ANO1, TMEM156, TMEM173, and TMEM213 correlated with patient survival. The four TMEMs were also upregulated in HPV-positive patients. The elevated expression of those TMEMs correlated with the enrichment of genes involved in cancer-related processes, including immune response. Specifically, overexpression of TMEM156 and TMEM173 was associated with immune cell mobilization and better survival rates, while the elevated ANO1 expression was linked with metastasis formation and worse survival. Conclusions: In this work, we performed a panel of in silico analyses to discover the role of TMEMs in head and neck squamous cell carcinoma. We found that ANO1, TMEM156, TMEM173, and TMEM213 correlated with clinical status and immune responses in HNSCC patients, pointing them as biomarkers for a better prognosis and treatment. This is the first study describing such the role of TMEMs in HNSCC. Future clinical trials should confirm the potential of those genes as targets for personalized therapy of HNSCC.

scholarly journals Tumor microenvironment and immune evasion in head and neck squamous cell carcinoma

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Areeg Elmusrati ◽  
Justin Wang ◽  
Cun-Yu Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
High Morbidity ◽  
Advanced Therapies

AbstractHead and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.

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.

Role of cytokines in head and neck squamous cell carcinoma

2006 ◽  
Vol 6 (9) ◽  
pp. 1195-1203 ◽  
Author(s):  
Ralph Pries ◽  
Stefan Nitsch ◽  
Barbara Wollenberg
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma

scholarly journals HOXB7 acts as an oncogenic biomarker in head and neck squamous cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiang Wu ◽  
Jin Li ◽  
Tingyuan Yan ◽  
Xueping Ke ◽  
Xin Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Expression Pattern ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Clinicopathological Parameters ◽  
Migration And Invasion ◽  
Connectivity Map

Abstract Background The homeobox gene Homeobox B7 (HOXB7) is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, migration and invasion. However, its expression pattern and oncogenic role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we aimed to explore the expression pattern of HOXB7, its clinical significance as well as functional roles in HNSCC. Methods HOXB7 mRNA expression in HNSCC was determined by data mining and analyses from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The protein abundance of HOXB7 was measured by immunohistochemistry in 119 primary HNSCC samples and associations between its expression and clinicopathological parameters and patient survival were evaluated. The pro-tumorigenic roles of HOXB7 in HNSCC were further delineated in vitro by loss-of-function assay. And a xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Connectivity Map (CMap) analysis was performed to identify bioactive small molecules which might be potential inhibitors for HOXB7. Results Bioinformatics analyses showed that HOXB7 mRNA was significantly overexpressed in 8 independent HNSCC datasets from TCGA and GEO databases. HOXB7 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with high pathological grade, advanced clinical stage, cervical node metastasis (P = 0.0195, 0.0152, 0.0300) and reduced overall and disease-free survival (P = 0.0014, 0.0007). Univariate and multivariate Cox regression analyses further revealed HOXB7 as an independent prognostic factor for patients’ overall survival. Moreover, HOXB7 knockdown significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in HNSCC cells, and resulted in compromised tumour growth in vivo. Furthermore, CMap (Connectivity map) analysis has identified three potential bioactive small molecule inhibitors (NU-1025, thiamine, vinburnine) for HOXB7 targeted therapy in HNSCC. Conclusions Our findings revealed that overexpression of HOXB7 was associates with tumour aggressiveness and unfavourable prognosis by serving a novel prognostic biomarker in HNSCC. Moreover, HOXB7 might be involved in the development and progression of HNSCC as an oncogene, and thereby might be a potential therapeutic target for HNSCC.

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