Expression of let-7i and miR-192 is associated with resistance to cisplatin-based chemoradiotherapy in patients with larynx and hypopharynx cancer

Abstract Objectives The majority of patients with locally advanced larynx or hypopharynx squamous cell carcinoma are treated with organ-preserving chemoradiotherapy (CRT). Clinical outcome following CRT varies greatly. We hypothesized that tumor microRNA (miRNA) expression is predictive for outcome following CRT. Methods Next-generation sequencing (NGS) miRNA profiling was performed on 37 formalin-fixed paraffin-embedded (FFPE) tumor samples. Patients with a recurrence-free survival (RFS) of less than 2 years and patients with late/no recurrence within 2 years were compared by differential expression analysis. Tumor-specific miRNAs were selected based on normal mucosa miRNA expression data from The Cancer Genome Atlas database. A model was constructed to predict outcome using group-regularized penalized logistic ridge regression. Candidate miRNAs were validated by RT-qPCR in the initial sample set as well as in 46 additional samples. Results Thirteen miRNAs were differentially expressed (p  Conclusion The combined miRNA expression and disease stage prediction model for CRT outcome is superior to using either factor alone. This study indicates NGS miRNA profiling using FFPE specimens is feasible, resulting in clinically relevant biomarkers.