Author(s)
Seth Michael Buryska, BS
Frank Ondrey, MD PhD
Affiliation(s)
University of North Dakota;
Abstract:
Educational Objective: At the conclusion of this presentation, the participants should be able to have a greater insight into a seminal genomic alteration associated with the development and progression of head and neck squamous cell carcinoma.
Objectives: Evaluate SNAI1 (Snail) and SNAI2 (Slug) expression in head and neck cancer development using the TCGA.
Study Design: Retrospective analysis of SNAI1/2 mRNA in NCI TCGA.
Methods: SNAI1/2 expression parameters were examined in 520+ HNSCC samples using the NCI cBio Portal and the UAB Cancer Data Analysis Portal (UALCAN).
Results: Neither SNAI1 or SNAI2 are in the top 150 overexpressed genes in HNSCC compared to normal tissue. However, SNAI2 and SNAI1 expression is increased in HNSCC compared to normal tissue (p < 1e-12, p=2.39e-4, respectively). SNAI2 expression is even greater in TP53 mutant populations compared to TP53 nonmutant (p=2.16e-5). SNAI2 is also increased in Asian populations compared to Caucasian and African American populations (p=0.04, 0.014). SNAI1 expression exhibited a stepwise increase comparing grade 1 vs 2 and grade 1 vs 3 tumors as well (p=2.17e-5, 4.99e-6). SNAI2 mRNA expression demonstrates strong positive correlation with TGF-ß, INHBA, and other pathways upregulated in HNSCC.
Conclusions: SNAI1 and SNAI2 are known potent embryological stimulators of epithelial to mesenchymal transition resulting in metastatic properties in head and neck cancer. Genomic analysis of SNAI1/2 mRNA expression data from 496 HNSCC samples involving 20,000+ genes demonstrates SNAI2 expression are most strongly correlated with TGF- ß and INHBA; two genes concomitantly upregulated in HNSCC. This genome based evidence of HNSCC tumor samples corroborates studies which postulate a potential link between INHBA, TGF- ß, and SNAI1/2 via Smad complex activation as well as inflammatory cytokine dysregulation. Henceforth, this genomic analysis may be found useful in further defining a potentially seminal multigenetic relationship driving recurrent and metastatic properties in HNSCC.