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

Abstract

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.

Integrated MicroRNA Network Analyses Identify a Poor-Prognosis Subtype of Gastric Cancer Characterized by the miR-200 Family

“…During EMT, gastric cancer cells with fibroblastic morphologic changes show increased migration and invasiveness as a result of decreased cell-cell adhesion, and the cells then acquire a spindle-shaped, highly motile fibroblast phenotype (28). Several studies have reported associations between EMT-related proteins and tumor metastasis and prognosis in gastric cancer (29)(30)(31). Generally, loss of epithelial proteins (such as E-cadherin and cytokeratin) and/or acquisition of mesenchymal proteins [such as b-catenin (nuclear) and N-cadherin] are associated with poor tumor differentiation, advanced stage, and poor outcome in gastric cancer (30), consistent with our findings.…”

Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review)

“…Liu et al (29) discovered that Twist is expressed much higher in gastric cancer tissues compared to adjacent normal tissues at mRNA and protein levels by means of RT-PCR and western blotting. Likewise, abnormal Twist expression related strongly to lower 5-year survival rates in patients of GC in the Ru et al study, yet, they emphasized that the significance disappears in cases of stage IV (30). Various examinations in vitro collaboratively implied the carciogenesis of Twist.…”

A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition

“…[21][22][23] Twist expression is positively correlated with the degree of infiltration and with lymphatic and distant metastasis; in addition, cancer patients with high Twist expression exhibit lower 5-year survival rates, suggesting that Twist may be a useful marker for evaluating the prognosis of gastric cancer. 24,25 Vichalkovski examined the interaction between Twist and Akt and found that activated Akt upregulated the expression of phosphorylated Twistl and subsequently alleviated the induction of p53 caused by chemotherapy-induced DNA damage, resulting in the inhibition of apoptosis. 26 Moreover, the levels of Twist and phosphorylated Akt are also positively correlated in oral squamous cell carcinoma.…”