Abstract 2016: MicroRNA expression subtypes in head and neck squamous cell carcinoma.
Authors: Walter Vonn , Hayes Neil , Du Ying , Wilkerson Matthew D. , Hayward Michele , Salazar Ashley , Yin Xiaoying 
Published: August 2014

Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose underlying etiology is unknown. Gene expression (GE) subtypes were detected in HNSCC by Chung et al. (Cancer Cell 2004) and validated in a recent study by our group. However, to the best of our knowledge no corresponding investigation of microRNA (miRNA) expression subtypes in HNSCC has been performed, as previous studies compared miRNA expression patterns in tumor and normal samples.

Techniques: After receiving informed consent, we obtained tumor samples from an incident surgical sample of HNSCC patients at the University of North Carolina Hospital. miRNA and GE assays were performed using Affymetrix GeneChip miRNA 1.0 and Agilent 44K Gene Expression platforms, respectively. miRNA expression subtypes were discovered using ConsensusClusterPlus, statistical significance of miRNA expression patterns was assessed with SigClust, SAM was used to identify differentially expressed miRNAs, and the miRBase and DAVID databases were used to identify target genes and enriched pathways.

Results: After applying quality control procedures, miRNA expression data was available for 103 patients and 830 hsa-miRNAs, while GE data was available for 138 patients and 15,597 genes. Both miRNA and GE data was available for 75 patients. Clinical data was available for all patients. Three miRNA expression subtypes were detected, and all pairwise comparisons of the expression patterns in the subtypes were statistically significant after performing a Bonferroni correction. The association between GE and miRNA expression subtypes was not statistically significant. Differentially expressed miRNAs were identified when expression in each subtype was compared to the remaining subtypes. Examples include miR-15a, which was underexpressed in one subtype and has been shown act as a tumor suppressor miRNA, as well as both miR-155 and miR-21, which were overexpressed in a different subtype and have been shown to have oncogenic effects. Target genes corresponding to each collection of differentially expressed miRNAs were also identified, and results from the DAVID functional annotation database suggest that a number of cancer-related pathways are enriched for each set of target genes. Pearson correlation coefficients were computed for expression of each differentially expressed miRNA and the expression of its target genes. Several statistically significant negative miR-target gene correlations were found after adjusting for multiple comparisons, including miR-15b and SOX5, miR-520e and VEGFA, as well as miR-98 and FRAS1.

Conclusion: miRNA expression subtypes of HNSCC provide a valuable method for categorizing tumors that complements known GE expression subtypes. Moreover, the subtypes identify known and novel miRs with tumor suppressor and oncogenic effects via their interaction with target genes.

Citation Format: Vonn Walter, Neil Hayes, Ying Du, Matthew D. Wilkerson, Michele Hayward, Ashley Salazar, Xiaoying Yin. MicroRNA expression subtypes in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2016. doi:10.1158/1538-7445.AM2013-2016