MicroRNA-based subtypes in head and neck squamous cell carcinoma. MicroRNA-based subtypes in head and neck squamous cell carcinoma

Highly coordinated, deregulated expressions of microRNAs (miRNA) have been implicated in the development of various cancers, including head and neck squamous cell carcinoma (HNSCC). Outside of HPV infection, molecular classification of HNSCC is lacking, and patient stratification by anatomical location and stage does not account for the heterogenous clinical courses seen. Previous studies have proposed molecular classifications based on gene expression, but none describe the role of microRNA expression in HNSCC subtyping. In this study, we identified reliable miRNA clusters that can be used to subclassify HNSCC tumors as well as other squamous tumors of other anatomic locations. An institutional discovery cohort was generated using miRNA expression data from microarrays, and this was validated using publicly available next-generation microRNA sequencing data from TCGA. Further analysis of these subtypes revealed distinct biological and clinical features of HNSCC tumors based on the miRNA expression profiles, which provides new insights into the pathogenesis and treatment of HNSCC. Overall design: A total of 115 tumor samples were considered. Quality control procedures were applied to microarray probe-level intensity files, and a total of 88 tumor arrays remained after removal of duplicate arrays, low-quality arrays, and arrays from non-HNSCC samples. Probe-level data was quantile normalized, and RMA expression values were used from probes matched to 825 mature microRNA sequences. Samples HN008 - HN159 were used to profile mRNA expression in a previous study (Series GSE39366).