Molecular Landscape of Oral Cancer in Young Adults

Abstract

Oral cancer (OC) is the most common cancer of the head and neck. Tongue cancer (TC) is the most frequently diagnosed form of OC and is characterized by a high aggressiveness and progression. OC and TC are considered diseases of the elderly, but the incidence among young patients (under 45 years) is increasing every year. The etiological factors and pathogenetic mechanisms of early-onset OC and TC remain unclear. In the present study, based on The Cancer Genome Atlas database, we analyzed the mutational profile, methylome, transcriptome, proteome, and microbiome of OC and TC in young adults (n = 127) compared with older patients. Early-onset OC and TC demonstrated a decrease in the mutation burden, activation of Rap1, PI3K-Akt, MAPK, cGMP-PKG signaling pathways and signaling of Fc-gamma R-mediated phagocytosis, and a specific microbiome profile. In contrast to OC, TC was characterized by activation of such signaling pathways as JAK-STAT, immune response to infectious and parasitic diseases, and PD-L1/PD-1-mediated immunosuppression and inhibition of phagocytosis signaling. The obtained results indicate that early-onset OC demonstrates molecular features different from those in elderly patients, while TC differs from OC in molecular profile and should probably be considered a separate clinical form.