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 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 Identification of Immune-related lncRNA Panel for Predicting Immune Checkpoint Blockade and Prognosis in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Chongchang Zhou ◽  
Guowen Zhan ◽  
Zhisen Shen ◽  
Yi Shen ◽  
Hongxia Deng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Risk Model ◽  
Low Risk ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Abstract Immunotherapy is changing head and neck squamous cell carcinoma (HNSCC) treatment pattern. According to the Chinese Society of Clinical Oncology (CSCO) guidelines, immunotherapy has been deemed as first-line recommendation for recurrent/metastatic HNSCC, marking that advanced HNSCC has officially entered the era of immunotherapy. Long non-coding RNAs impact every step of cancer immunity. Therefore, reliable immune-lncRNA able to accurately predict the immune landscape and survival of HNSCC are crucial to clinical management. In the current study, we downloaded the transcriptomic and clinical data of HNSCC from The Cancer Genome Altas and identified differentially expressed immune-related lncRNAs (DEir-lncRNAs). Further then, Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to identify proper DEir-lncRNAs to construct optimal risk model. Low-risk and high-risk groups were classified based on the optimal cut-off value generated by the areas under curve for receiver operating characteristic curves (AUC), and Kaplan-Meier survival curves were utilized to validate the prediction model. We then evaluated the model based on the clinical factors, immune cell infiltration, chemotherapeutic and immunotherapeutic efficacy between two groups. Our results constructed a risk model consisted of 18 DEir-lncRNA pairs showing significantly association with survival of patients with HNSCC. Besides, HNSCC patients with low risk score significantly enriched of CD8+ T cell, and corelated with high chemosensitivity and immunotherapeutic sensitivity. In summary, our risk model could be served as a promising clinical prediction indicator, effective discoursing of the immune cell infiltration of HNSCC patients, and distinguishing patients who could benefit from chemotherapy and 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 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.

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