Potential Roles of Activin in Head and Neck Squamous Cell Carcinoma Progression and Mortality.

Abstract

Activin, a member of the TGF-β super family of cytokines, is involved in head and neck squamous cell carcinoma (HNSCC). This study examined the constituents of the activin axis in order to further elucidate the role of activin A in HNSCC progression. Immunohistochemistry (IHC), reverse transcription polymerase chain reaction (RT-PCR), MTT, and matrigel invasion assays, in addition to analysis of the tumor cancer genome atlas (TCGA), were employed. IHC in HNSCC and oral leukoplakia (OPL) lesions demonstrated increased expression of the inhibin subunit βA (INHBA) (p<0.0001), as well as activin receptor type IB (ACVR1B) (p<0.0032) compared to normal mucosa. TCGA analysis revealed increased INHBA expression was associated with lymph node positive tumors (p=0.024), decreased overall survival (p=0.0167), and decreased promoter methylation (p<0.0001). Concomitant up-regulated expression of gene pathways strongly correlated with INHBA expression demonstrated further deleterious effects on survival (p<0.0148). Activin may be an important component of early carcinogenesis in OPL and HNSCC with unfavorable effects on clinical end-points such as survival.