Expression Analysis Elucidates the Roles of MAML1 and Twist1 in Esophageal Squamous Cell Carcinoma Aggressiveness and Metastasis

Abstract

Epithelial-mesenchymal transition has recently attracted great attention in studying the malignant progression of cells through a converging pathway of oncogenesis and metastasis. Twist1 and Mastermind-like 1 (MAML1) are major regulators of EMT through different pathways. The aim of this study was to investigate the clinicopathological relevance of the expression of MAML-1 and Twist1 genes in esophageal squamous cell carcinoma (ESCC). Tumoral and corresponding normal tissues from 55 treatment-naive ESCC patients were subjected for expression analysis with quantitative real-time RT-PCR. Overexpression of MAML-1 and Twist1 were significantly associated with lymph node metastasis and the surgical staging of tumor. Overexpression of Twist1 was associated with tumor depth of invasion. Mean relative expression (MRE) of MAML1 was significantly higher in patients with metastasis to lymph nodes (3.07 ± 0.51 vs. 0.86 ± 0.58, P = .008). MRE of Twist1 was significantly higher in patients with invasion of tumor to adventitia (T3, T4) (1.97 ± 0.29 vs. 0.39 ± 0.73, P = .036). In advanced stages of tumor (stage III, IV), a significantly higher MRE of Twist1 (2.47 ± 0.41 vs. 1.25 ± 0.36, P = .035) and MAML1 (3.05 ± 0.45 vs. 1.07 ± 0.59, P = .021) mRNA was observed. We introduce Twist1 and MAML1 as new molecular markers of advanced tumor, which determine the characteristics and aggressive behavior of ESCC. Along with the emerging evidence of their role in different cellular processes and aberrations in various cancers, they are suggested as potentially interesting therapeutic targets to reverse a broad spectrum of functional aberrations that promote ESCC development.