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

Purpose: TWIST 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.

Methods: upper 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).

Results: Survival 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.

Conclusions: TWIST1 and TWIST2 are differentially associated with HNSCC patient survival. Gender and smoking could modify the effect of TWIST s on the risk of death in HNSCC patients.