Prognostic values and clinical relationship of TYK2 in laryngeal squamous cell cancer

Fang, Lucheng; Wang, Wen; Shi, Licai; Chen, Qinjuan; Rao, Xingwang

doi:10.1097/md.0000000000027062

Cited by 3 publications

(5 citation statements)

References 45 publications

(86 reference statements)

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“…A previous study on laryngeal squamous cell carcinoma found that lower TYK2 would be significantly associated to worse overall survival ([ 24 ]), which is in line with the current analysis. Thereby, it was reported that the expression of TYK2 was associated with lymph node status and metastasis ([ 24 ]). This is in line with the results of univariate analysis in the current study, confirming metastasis formation, lymph nodular status, and TYK2 expression to be predictors of survival.…”

Section: Discussionsupporting

confidence: 92%

“…In esophageal squamous cell carcinoma, TYK2 was also confirmed to be overexpressed, serving as an oncogene ([ 23 ]). Similar results were found for laryngeal squamous cell carcinoma ([ 24 ]). Therefore, the overexpression of TYK2 in HNSC appears a reasonable and expectable finding of the current study.…”

Section: Discussionsupporting

confidence: 88%

“…Survival is a critical outcome parameter of HNSC; thereby, majority of recurrence or disease-specific deaths take place within 2-3 years since diagnosis ([ 25 ]). TYK2 has previously been found to be related to autoimmunity ([ 15 – 17 ]) and various cancers ([ 24 , 26 , 27 ]). A previous study on laryngeal squamous cell carcinoma found that lower TYK2 would be significantly associated to worse overall survival ([ 24 ]), which is in line with the current analysis.…”

Section: Discussionmentioning

confidence: 99%

“…TYK2 has previously been found to be related to autoimmunity ([ 15 – 17 ]) and various cancers ([ 24 , 26 , 27 ]). A previous study on laryngeal squamous cell carcinoma found that lower TYK2 would be significantly associated to worse overall survival ([ 24 ]), which is in line with the current analysis. Thereby, it was reported that the expression of TYK2 was associated with lymph node status and metastasis ([ 24 ]).…”

Section: Discussionmentioning

confidence: 99%

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Identification of Gene-Tyrosine Kinase 2 (TYK2) in Head and Neck Squamous Cell Carcinoma Patients—An Integrated Bioinformatics Approach

Gong

Ren

2022

Disease Markers

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Background. The human tyrosine kinase 2 (TYK2) has been found to be associated with at least 20 autoimmune diseases; however, its tumor-regulating role in head and neck squamous cell carcinoma (HNSC) has not been researched by using an integrative bioinformatics approach, yet. Objective. To investigate the regulating mechanisms of the TYK2 gene in HNSC in terms of its expression pattern, prognostic values, involved biological functions, and implication of tumor immunity. Methods. The TYK2 gene expression pattern and regulatory involvement in HNSC were investigated using publically accessible data from TCGA database. R software tools and public web servers were utilized to conduct statistical analysis on cancer and noncancerous samples. Results. TYK2 was found to be significantly upregulated in HNSC samples compared with healthy control samples. The expression of TYK2 gene was shown to be associated with the prognosis of HNSC by showing its upregulation represented better survival outcome. The regulating role of TYK2 in HNSC was found mainly in several pathways including DNA replication, base excision repair, apoptosis, p53 signaling pathway, and NF-kappa B signaling pathway. The gene set enrichment analysis (GSEA) results showed that TYK2-significantly correlated genes were mainly enriched in several biological functional terms including cell cycle, DNA replication, PLK1 pathway, ATR pathway, and Rho GTPase pathway. In addition, TYK2 was found to be involved in tumor immunity, showing positive correlation with the majority of tumor infiltrating immune cells, immune checkpoint genes, and significant representative components of tumor microenvironment, according to the ESTIMATE-Stromal-Immune score. Conclusions. Given the dysregulation, prognostic values, regulating tumor progression-related pathways, and the tumor immune-modulatory role of TYK2 in HNSC, the TYK2 gene should be regarded as a potential therapeutic target in treating head and neck cancer.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Identification of Gene-Tyrosine Kinase 2 (TYK2) in Head and Neck Squamous Cell Carcinoma Patients—An Integrated Bioinformatics Approach

Gong

Ren

2022

Disease Markers

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“…Tyrosine kinase 2 (TYK2), a member of the Janus kinase (JAK) family, has emerged as both a promising biomarker and a target for anticancer therapies (Borcherding et al, 2021). It has been reported that high expression of TYK2 is associated with better prognosis of HNSCC (Fang et al, 2021). A recent review concluded that CC motif chemokine receptor (CCR7) is correlated with good outcomes of HNSCC patients (Korbecki et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

8-Gene signature related to CD8+ T cell infiltration by integrating single-cell and bulk RNA-sequencing in head and neck squamous cell carcinoma

Zhang

Zhang²,

Zhang³

2022

Front. Genet.

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Background: CD8+ T cells, a critical component of the tumor immune microenvironment, have become a key target of cancer immunotherapy. Considering the deficiency of robust biomarkers for head and neck squamous cell carcinoma (HNSCC), this study aimed at establishing a molecular signature associated with CD8+T cells infiltration.Methods: Single-cell RNA sequencing data retrieved from the Gene Expression Omnibus (GEO) database was analyzed to obtain the different cell types. Next, the cell proportions were investigated through deconvolution of RNA sequencing in the Cancer Genome Atlas (TCGA) database, and then the immune-related genes (IRGs) were identified by weighted gene co-expression network analysis (WGCNA). LASSO-Cox analysis was employed to establish a gene signature, followed by validation using a GEO dataset. Finally, the molecular and immunological properties, and drug responses between two subgroups were explored by applying “CIBERSORT”, “ESTIMATE”, and single sample gene set enrichment analysis (ssGSEA) methods.Results: A total of 215 differentially expressed IRGs were identified, of which 45 were associated with the overall survival of HNSCC. A risk model was then established based on eight genes, including DEFB1, AICDA, TYK2, CCR7, SCARB1, ULBP2, STC2, and LGR5. The low-risk group presented higher infiltration of memory activated CD4+ T cells, CD8+ T cells, and plasma cells, as well as a higher immune score, suggesting that they could benefit more from immunotherapy. On the other hand, the high-risk group showed higher abundance of activated mast cells and M2 macrophages, as well as a lower immune score.Conclusion: It was evident that the 8-gene signature could accurately predict HNSCC prognosis and thus it may serve as an index for clinical treatment.

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Development and Validation of a Necroptosis-Related Prognostic Model in Head and Neck Squamous Cell Carcinoma

Zhi-jing

Qiu

et al. 2022

Journal of Oncology

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Necroptosis is a new regulated cell-death mechanism that plays a critical role in various cancers. However, few studies have considered necroptosis-related genes (NRGs) as prognostic indexes for cancer. As one of the most common cancers in the world, head and neck squamous cell carcinoma (HNSCC) lacks effective diagnostic strategies at present. Hence, a series of novel prognostic indexes are required to support clinical diagnosis. Recently, many studies have confirmed that necroptosis was a key regulated mechanism in HNSCC, but no systematic study has ever studied the correlation between necroptosis-related signatures and the prognosis of HNSCC. Thus, in the current study, we aimed to construct a risk model of necroptosis-related signatures for HNSCC. We acquired 159 NRGs from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and compared them with samples of normal tissue downloaded from The Cancer Genome Atlas (TCGA), ultimately screening 38 differentially expressed NRGs (DE-NRGs). Then, by Cox regression analysis, we successfully identified 7 NRGs as prognostic factors. We next separated patients into high- and low-risk groups via the prognostic model consisting of 7 NRGs. Individuals in the high-risk group had much shorter overall survival (OS) times than their counterparts. Furthermore, using Cox regression analysis, we confirmed the necroptosis-related prognostic model to be an independent prognostic factor for HNSCC. Receiver operating characteristic (ROC) curve analysis proved the predictive ability of this model. Finally, Gene Expression Omnibus (GEO) data sets (GSE65858, GSE4163) were used as independent databases to verify the model’s predictive ability, and similar results obtained from two data sets confirmed our conclusion. Collectively, in this study, we first referred to necroptosis-related signatures as an independent prognostic model for cancer via bioinformatics measures, and the necroptosis-related prognostic model we constructed could precisely forecast the OS time of patients with HNSCC. Utilizing the model may significantly improve the diagnostic rate and provide a series of new targets for treatment in the future.

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Prognostic values and clinical relationship of TYK2 in laryngeal squamous cell cancer

Abstract: Supplemental Digital Content is available in the text

Cited by 3 publications

References 45 publications

Identification of Gene-Tyrosine Kinase 2 (TYK2) in Head and Neck Squamous Cell Carcinoma Patients—An Integrated Bioinformatics Approach

Identification of Gene-Tyrosine Kinase 2 (TYK2) in Head and Neck Squamous Cell Carcinoma Patients—An Integrated Bioinformatics Approach

8-Gene signature related to CD8+ T cell infiltration by integrating single-cell and bulk RNA-sequencing in head and neck squamous cell carcinoma

Development and Validation of a Necroptosis-Related Prognostic Model in Head and Neck Squamous Cell Carcinoma

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