Molecular features of T and N stage progression in laryngeal cancer

Laryngeal squamous cell cancer (LSCC) is a common type of head and neck cancer that is typically unrelated to human papilloma virus (HPV) infection. Late-stage laryngeal cancers are associated with greater morbidity due to obstructive symptoms, and poorer overall survival. Using data from The Cancer Genome Atlas (TCGA), we analyzed 112 patient LSCC samples, comparing patient proteome, transcriptome and genome between early and late T and N samples. We observed significant differences in SNV frequency for various genes between the early and late-stage groups. Most notably we observed that NOTCH1 mutation, which was more frequent in late N-stage supraglottic cancers, was also associated with poorer patient survival in LSCCs. Methylation analysis also revealed changes in JUN gene methylation in late N glottic cancers. Transcriptomic analysis revealed differential expression in c-JUN, HOXB7 and HOXB9 transcript levels, suggesting potential involvement of these pathways in progression and nodal involvement. Our findings illustrate that LSCC undergoes distinct molecular changes associated with different stages and subsites. We observed multiple potential markers for progression, metastases and survival, including NOTCH1 mutation, which may aid as prognostic indicators in future studies.