Transcriptional subtypes of glottic cancer characterized by differential activation of canonical oncogenic programming.

BACKGROUND: There is a paucity of data concerning molecular heterogeneity among glottic squamous cell carcinoma, and the clinical implications thereof.

METHODS: Data corresponding to glottic squamous cell carcinoma were derived from The Cancer Genome Atlas. The Onco-GPS computational methodology was levied to derive four patterns of transcriptional activity and three functional subtypes of glottic cancer.

RESULTS: Thirty glottic cancer samples stratified to three distinct oncogenic states (S0-S2) based on a Onco-GPS model containing four transcriptional components (F0-F3). Membership in S2 and association with transcriptional component F0 conveyed an invasive phenotype, with transcriptional activity strongly reflecting EMT programming (including TGF-B and NF-KB signaling). S2 membership also correlated with inferior disease-specific survival (HR 9.027, 95% CI 1.021-79.767), and higher incidences of extracapsular spread and perineural invasion.

CONCLUSIONS: We present a functional taxonomy of glottic cancer, with subtypes demonstrating differential upregulation of canonical oncogenic networks and survival implications.