Association between cancer stem cell gene signature and prognosis in head and neck squamous cell carcinoma

Background: Various cancer stem cell (CSC) biomarkers and genes encoding them in head and neck squamous cell carcinoma (HNSCC) have been identified and evaluated. However, the validity of these factors in the prognosis of HNSCC has been questioned and remains to be ascertained. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC by using five publicly available HNSCC cohorts. Methods: To predict the prognosis of patients with HNSCC, we developed and validated CSC gene signatures whose mRNA expression was correlated with at least one of four CSC genes, CD44, MET, ALDH1A1, and BMI1. Results: Patients in TCGA HNSCC cohort were classified into CSC gene-associated high-risk (CSC-HR; n=285) and CSC gene-associated low-risk (CSC-LR; n=281) subgroups. The 5-year overall survival and recurrence-free survival rates were significantly lower in the CSC-HR subgroup than in the CSC-LR subgroup (p=0.04 and 0.02, respectively). The clinical significance of the CSC gene signature was validated using four independent cohorts. Cox proportional hazards models showed that the CSC gene signature was an independent prognostic factor for patients with HNSCC. Furthermore, CSC gene signature was associated with the prognosis of patients with HNSCC who received radiotherapy or those with HPV (-) status. Conclusion: The CSC gene signature was associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC.