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

Abstract

Background Various cancer stem cell (CSC) biomarkers and the 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 unclear. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC, using five publicly available HNSCC cohorts. Methods To predict the prognosis of patients with HNSCC, we developed and validated the expression signatures of CSC biomarker genes whose mRNA expression levels correlated with at least one of the four CSC genes (CD44, MET, ALDH1A1, and BMI1). Results Patients in The Cancer Genome Atlas (TCGA) HNSCC cohort were classified into CSC gene expression-associated high-risk (CSC-HR; n = 285) and CSC gene expression-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 expression signature was validated using four independent cohorts. Analysis using Cox proportional hazards models showed that the CSC gene expression signature was an independent prognostic factor of non-oropharyngeal HNSCC which mostly indicates HPV (–) status. Furthermore, the CSC gene expression signature was associated with the prognosis of HNSCC patients who received radiotherapy. Conclusion The CSC gene expression signature is associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC, especially in cases with HPV (–) status who were classified in more detail.

Cancer-associated fibroblast-derived extracellular vesicles promote lymph node metastases in oral cavity squamous cell carcinoma by encapsulating ITGB1 and BMI1

“…BMI1 was revealed to be a prognostic indicator for brain tumors, lung adenocarcinoma, gastric cancer, renal cell carcinoma, colorectal cancer, and ovarian cancer [ 22 ]. Kim et al showed that BMI1 was one of the four cancer stem cell-related genes in head and neck SCC that were associated with patient prognosis [ 23 ]. More relevantly, Kurihara et al revealed that the protein and mRNA expression of BMI1 occurred during the invasion of patients with tongue SCC [ 24 ].…”

De-escalated radiation for human papillomavirus virus-related oropharyngeal cancer: evolving paradigms and future strategies

“…The potential of high-yield, next generation sequencing panels to cluster tumors into even more distinct subtypes based on immunogenomics has also been described ( 110 , 111 ). Others have suggested that expression of cancer stem cell markers in HPV-positive oropharyngeal squamous may help further characterize biological behavior and identify patients who derive the most benefit from de-escalation ( 112 ). Indeed, attempts to discern gene profile signatures that might be useful for risk stratification continue to be explored ( 113 ).…”