Smoking and gender modify the effect of TWIST on patient survival in head and neck squamous carcinoma

Abstract

PurposeTWIST is a critical factor for predicting prognosis in several human cancers. Here, we study the prognostic significance of TWIST1 and TWIST2 in Head and Neck squamous cell carcinoma (HNSCC) as well as interactions of TWISTs with both gender and smoking in patient survival.Methodsupper quartile normalized RNA-seq V2 RSEM values of TWIST1 and TWIST2 expressions were retrieved from a TCGA HNSCC dataset. Kaplan-Meier survival curves were used to assess the associations of TWIST1 and TWIST2 with patient survival, and multivariate Cox proportional hazards regression models were used to estimate the hazards ratios (HRs) and their 95% confidence intervals (CIs).ResultsSurvival analyses showed that high TWIST1 expression was associated with a poor overall survival at a borderline significance level, while a superior but not statistically significant overall survival was observed in high TWIST2 expression. The multivariate Cox proportional hazards regression model showed a significantly elevated risk of death (HR=1.37, p = 0.038) in patients with high TWIST1 compared to low TWIST1, and a borderline significantly decreased risk of death (HR = 0.74, p = 0.055) in patients with high TWIST2 compared to low TWIST2. Further stratification analyses showed that increased risks of death were found significantly in male and borderline significantly in smoker patients with high TWIST1 compared to low one, and a significantly decreased risk of death in non-smoker patients with high TWIST2 compared to low one.ConclusionsTWIST1 and TWIST2 are differentially associated with HNSCC patient survival. Gender and smoking could modify the effect of TWISTs on the risk of death in HNSCC patients.

<p>DNA methylation-mediated Klotho silencing is an independent prognostic biomarker of head and neck squamous carcinoma</p>

“…KL has also been reported to inhibit TGF-β1-induced epithelial–mesenchymal transition (EMT) by directly binding to TGF-β receptor 29. Our previous study revealed that high expression of TWIST1, a key regulator in EMT, was associated with poor survival in HNSCC 30. In this study, we observed a significantly positive relationship between KL mRNA levels and the overall survival of HNSCC patients.…”

Differential expression of lung adenocarcinoma transcriptome with signature of tobacco exposure

“…Further studies by Zhu et al investigating TWIST interactions with gender and smoking in patient survival revealed that both smoking and gender could modify the effects on the risk of death in HNSCC patients. Their analysis revealed that TWIST1 links to poor survival obvious in either males or smokers than in either female or non-smokers (Zhu et al 2017 ). Additionally, Stoyianni et al used cancers of unknown primary (CUP) as a model for metastatic dissemination to study the prognostic significance of EMT.…”

Methylation-Driven Genes Identified as Novel Prognostic Indicators for Thyroid Carcinoma

“…It is commonly believed that epigenetic changes, such as DNA methylation, can drive abnormal gene expression of crucial genes involved in the development and progression of cancer, including prostate cancer (Chen et al, 2014), liver cancer (Feitelson, 2006), head and neck cancer (Worsham et al, 2014), etc. In addition, previous studies also reported that the methylation status of specific genes significantly associated with worse prognosis (Lee et al, 2006;Zhu et al, 2017). Therefore, the methylation-driven genes could serve as attractive prognostic indicator in tumor patients.…”