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Previous reports indicate that Cdc42-interacting protein-4 (CIP4) has previously been reported to plays an important role in the progression of various cancers. However, its correlation with laryngeal cancer (LC) remains unreported. Data from TCGA and GEO databases were used to evaluate the role of CIP4 in LC. Based on GEO and TCGA datasets, we analyzed the differences in CIP4 expression between normal and tumor samples. The Wilcoxon signed-rank test was used to analyze the relationship between clinical features and CIP4. Cox regression and the Kaplan-Meier analyses were used to identify the clinical characteristics associated with the overall survival. Also, the GEPIA database was used to confirm the relationship between CIP4 and overall survival. Lastly, Gene Set Enrichment Analysis (GSEA) was performed based on the TCGA dataset. CIP4 expression in LC was significantly associated with gender and tumor stage (p-values<0.05). Similar to GEPIA validation, Kaplan-Meier survival analysis demonstrated that LC with CIP4-low exhibited a worse prognosis than that with CIP4-high. Univariate analysis revealed that CIP4-high significantly correlated with better overall survival (HR: 0.522, 95% CI: 0.293-0.830, P = 0.026). Besides, multivariate analysis revealed that CIP4 remained independently associated with the overall survival (HR: 0.61, 95% CI: 0.326-0.912, P = 0.012). GSEA showed that the p53, WNT signaling, TGF-β signaling pathways, etc. were enriched in a phenotype high CIP4 expression. In summary, the CIP4 gene is a potential prognostic molecular marker for patients diagnosed with laryngeal cancer. Moreover, the p53, WNT signaling, and TGF-β signaling pathways are potentially associated with CIP4 in LC., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients with a prior history of cancer are commonly excluded from clinical trial. Increasing number of studies implied that a prior cancer did not adversely affect the clinical outcome among various types of cancer patients. However, the impact of prior cancer on survival of larynx cancer patients remains largely unknown. The aim of this study was to evaluate the prevalence of prior cancer and assess its impact on survival of patients diagnosed with larynx cancer., Methods: Patients with larynx cancer as the first or second primary malignancy diagnosed from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier method, multivariate Cox proportional hazard model, and multivariate competing risk model were performed for survival analysis., Results: A total of 24,812 eligible patients with larynx cancer were included in the study, wherein a total of 2436 patients (9.8%) had a prior history of cancer. Prostate (36%), lung and bronchus (10%), urinary bladder (7%), and breast (6%) were the most common types of prior cancer. A prior cancer history served as a risk factor for overall survival (AHR =1.30; 95% CI [1.21-1.41]; P < 0.001) but a protective factor for cancer-specific mortality (AHR = 0.83; 95% CI [0.72-0.94]; P = 0.004) in comparison with those without prior cancer. The subgroup analysis showed that a prior history of cancer adversely affected overall survival of patients with larynx cancer in most subgroups stratified by timing and types of prior cancer, as well as by different clinicopathologic features., Conclusion: Our study indicated an adverse survival impact of a prior history of cancer on patients with larynx cancer. Except for a few particular prior cancer, clinical trials should be considered prudently for laryngeal cancer patients with prior cancers.