MAML1 and TWIST1 co-overexpression promote invasion of head and neck squamous cell carcinoma.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with considerable morbidity and mortality. Invasion and metastasis of HNSCC is a complex process involving multiple molecules and signaling pathways. Twist FamilyBHLHTranscription Factor 1 (TWIST1) and Mastermind-like 1 (MAML1) are essential in induction of epithelial-mesenchymal transition through direct regulation of implicated molecules in cellular adhesion, migration and invasion. Our aim in this study was to assess the clinical significance of MAML1 and TWIST1 expression in HNSCC, and elucidate the probable correlation between these genes to exhibit their possible associations with progression and metastasis of the disease. The gene expression profile of MAML1 and TWIST1 was assessed in fresh tumoral compared to distant tumor-free tissues of 55 HNSCC patients using quantitative real-time Polymerase chain reaction (PCR). Significant overexpression of MAML1 and TWIST1 mRNA was observed in 49.1% and 38.2% (P˂0.05) of tumor specimens, respectively. Overexpression of MAML1 was associated with vascular invasion (P=0.048). Concomitant overexpression of MAML1 and TWIST1 was significantly correlated to each other (P=0.004). Co-overexpression of the genes was significantly correlated to the various clinicopathological indices of poor prognosis including depth of tumor invasion (P<0.01), lymphatic invasion and grade of tumor cell differentiation (P<0.05). Significant correlation between MAML1 and TWIST1 in HNSCC was revealed. This study was the first report elucidating MAML1 clinical relevance in HNSCC. These new findings suggest an oncogenic role for concomitant expression of MAML1 and TWIST1 genes in HNSCC invasion and metastasis.