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

Head Neck. 2023 Nov;45(11):2851-2861. doi: 10.1002/hed.27514. Epub 2023 Sep 8.

Abstract

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.

Keywords: epithelial-to-mesenchymal transition; glottic squamous cell carcinoma; molecular determinants of clinical outcomes; survival differences in glottic cancer; transcriptional subtypes.

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Glottis / pathology
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Laryngeal Neoplasms* / pathology
  • Neoplasm Staging
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Tongue Neoplasms* / pathology