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

•Small RNA profiling using FFPE samples from patients with head and neck cancer.•miRNAs are differentially expressed between patients with poor and good response.•Let-7i and miR-192 with clinical stage may be predictive for clinical outcome. 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. 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. Thirteen miRNAs were differentially expressed (p