Expression of Twist, Slug and Snail in esophageal squamous cell carcinoma and their prognostic significance

Abstract

Esophageal cancer is one of the most common types of malignancy worldwide. At present, surgical resection is the main treatment for esophageal cancer, but recurrence and distant metastasis are the main causes of mortality. The transcription factors Twist, Slug and Snail regulate epithelial-mesenchymal transition and thereby participate in tumor invasion and metastasis. The aim of the present study was to investigate the expression of Twist, Slug and Snail in esophageal squamous cell carcinoma (ESCC) and their prognostic significance. The expression of Twist, Slug and Snail in 229 paraffin-embedded ESCC and matched normal mucosal tissues was detected by immunohistochemistry. The expression differences of Twist, Slug and Snail in the ESCC and normal tissues were compared by χ 2 test, and the associations between the three proteins and the clinicopathological parameters of ESCC were analyzed. The expression levels of Twist, Slug and Snail in 29 fresh frozen ESCC and matched normal mucosal tissues were detected by reverse transcription-quantitative PCR. The correlations among Twist, Slug and Snail in ESCC were examined by Pearson's correlation analyses. In addition, single factor and multivariate Cox regression analyses were used to analyze the influence of Twist, Slug and Snail on the prognosis of ESCC. Twist was found to be highly expressed in ESCC. The difference of Slug expression in ESCC was associated with differentiation degree, TNM stage and vascular invasion, but no significant association was observed between Snail expression and any clinicopathological parameters. In ESCC, there were significant differences in protein expression between Twist and Snail, and Slug and Snail. The mRNA expression level of Twist in ESCC was significantly higher than that in normal esophageal mucosa. However, the mRNA expression of Slug in normal esophageal mucosa was higher than that in ESCC, and the mRNA expression levels of Twist and Snail were positively correlated in ESCC. Kaplan-Meier analysis of 229 patients with ESCC revealed that Snail influenced the overall survival, as did the co-expression of Twist and Snail. Nerve invasion was also identified as an independent factor affecting the progression-free survival of ESCC. The results indicate that Twist is highly expressed, Slug may be a tumor suppressor, and Snail is an independent prognostic factor in ESCC. Twist and Snail are positively correlated, and the simultaneous inhibition of Twist and Snail protein expression may be beneficial for prolonging the overall survival of patients with ESCC.

Prognostic and clinicopathological value of Twist expression in esophageal cancer: A meta-analysis

“…The baseline characteristics of the included studies are shown in Table 1 . Among all eligible studies, six studies were published in English[ 11 - 14 , 17 , 18 ], while five were published in Chinese[ 15 , 16 , 19 - 21 ]. All included studies examined the expression of Twist in esophageal cancer tissue with immunohistochemistry (IHC).…”

“…All included studies examined the expression of Twist in esophageal cancer tissue with immunohistochemistry (IHC). Two metrics for IHC staining were used in some studies[ 11 , 12 , 18 - 21 ]: The percentage of positively stained cells and the staining intensity. However, some studies[ 13 - 17 ] evaluated Twist expression using only one metric for IHC staining, which resulted in assessing the expression of Twist at various cutoff values.…”

“…The prognostic value of Twist in esophageal cancer has been investigated in many studies[ 11 - 21 ] with controversial results. Some studies[ 12 , 13 , 15 , 17 ] have shown that Twist overexpression is closely related to the poor prognosis of esophageal cancer, while others show that it is unrelated[ 11 , 14 , 16 , 18 - 21 ]. Therefore, we performed a meta-analysis to combine relevant studies and clarify whether Twist could be a promising biomarker for predicting prognosis in esophageal cancer.…”

HuR Affects the Radiosensitivity of Esophageal Cancer by Regulating the EMT-Related Protein Snail

“…found that Snail is an independent risk factor for the prognosis of patients with esophageal cancer. The combination of Snail and Twist can significantly affect the overall survival rate of patients with esophageal cancer ( 38 ). It has also been reported that Snail is involved in the regulation of radiosensitivity in esophageal cancer.…”

The Role and Interactions of Programmed Cell Death 4 and its Regulation by microRNA in Transformed Cells of the Gastrointestinal Tract

“…However, it was found that PDCD4 directly interacts with the basic helix-loop-helix (bHLH) transcription factor Twist ( 66 ), a protein which has been attributed to having a role in mesoderm formation, myogenesis, neurogenesis and neural crest cell migration and differentiation ( 67 ), as well as endowing stem cell characteristics in tumour cells and promoting EMT ( 68 ). Twist has increased expression in oesophageal squamous cell carcinomas ( 69 ), is associated with gastric cancer progression ( 70 ) and increased proliferation and invasion in CRC ( 71 ). PDCD4 binding to twist results in the down regulation of the Twist target, Y-Box binding protein 1 (TB-1) and consequently a reduction in cell growth ( 66 ).…”