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

Abstract

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.