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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Prognostic values and clinical relationship of TYK2 in laryngeal squamous cell cancer
Lucheng Fang1, Wen Wang1, Licai Shi1
1First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, China.
Abstract:
Laryngeal squamous cell cancer (LSCC) is the second most common head and neck cancer with the increasing mortality. The tyrosine kinase 2 (TYK2) has previously been reported to play an important role in various cancers excepting LSCC. We used available data from the cancer genome atlas program (TCGA), gene expression omnibus, and gene expression profiling interactive analysis (GEPIA) to evaluate the role of TYK2 in LSCC.The difference of TYK2 expression level between normal and tumor samples was analyzed based on TCGA, gene expression omnibus, and GEPIA databases. The relationship between clinical features and TYK2 were analyzed using the Wilcoxon signed-rank test. We applied Cox regression and the Kaplan-Meier method to finding which clinical characteristics is associated with overall survival. Also, we used GEPIA database to validate the relationship between TYK2 and overall survival. At last, we performed gene set enrichment analysis based on TCGA data set.The expression level of TYK2 in LSCC was significantly associated with gender, lymph node status and metastasis (P-values <.05). Kaplan-Meier survival analysis, as same as GEPIA validation, demonstrated that LSCC with TYK2-low had a worse prognosis than that with TYK2-high. The univariate analysis showed that TYK2-high correlated significantly with a better overall survival (hazard ratio: 0.351, 95% confidence interval: 0.194-0.637, P < .001). The multivariate analysis revealed that TYK2 remained independently associated with overall survival (hazard ratio: 0.36, 95% confidence interval: 0.185-0.699, P = .003). Gene set enrichment analysis shows that Janus kinases-STAT signaling pathway, p53 signalling pathway and natural killer cell mediated cytotoxicity, etc are enriched in TYK2 high expression phenotype.Gene TYK2 may be a potential prognostic molecular marker for LSCC. Moreover, the Janus kinases-STAT signaling pathway and p53 signaling pathway are probably the key pathway associated with TYK2 in LC.
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