Upregulation of Twist in Gastric Carcinoma Associated with Tumor Invasion and Poor Prognosis

Tumor invasion and metastasis are the most common causes of death in gastric carcinoma. Twist, a transcription factor of the basic helix-loop-helix class, reportedly regulates cancer metastasis and induces epithelial-mesenchymal transition (EMT). We evaluated the expression of Twist and its effect on cell migration in gastric carcinoma (GC). Twist expression was detected by real-time quantitative RT-PCR in gastric tumor tissue, metastatic lymph nodes and normal gastric tissue from 47 gastric carcinoma patients who had undergone gastrectomies with radical lymph node dissections without preoperative treatment. Twist expression was also analyzed immunohistochemically in 436 gastric cancer cases. GC tumor tissue and metastatic lymph nodes was upregulated compared with normal gastric mucosa (P < 0.05). Twist protein expression differed significantly among gastric tumor tissue, matched normal gastric mucosa, and lymph nodes (P < 0.05) In stages I, II, and III, 5-year survival rates of patients with high Twist expression were significantly lower than in patients with low expression (P < 0.05). In stage IV, Twist expression did not correlate with 5-year survival rates (P = 0.07). Further multivariate analysis suggested that depth of invasion, lymph-node and distant metastases, TNM stage, and up-regulation of TWIST were independent prognostic indicators for GC. Twist expression in gastric cancer is associated significantly with lymph-node and distant metastases, and poor prognosis. Twist may be a useful marker for the development, progression and metastasis of GC.