Zinc finger E-box-binding homeobox 1 (ZEB1): A novel predictor for the prognosis in gastrointestinal tumors.

Abstract

e23515 Background: The gastrointestinal stromal tumors (GISTs) are the most common soft tissue sarcoma arising anywhere along gastrointestinal tract. The advanced and metastatic GISTs are the leading cause in GISTs inducing death. GISTs are the most commonly resulted from KIT or PDGFRA activation mutation. Currently adjuvant therapy with imatinib also targets the KIT and PDGFRA signals, which significantly increases the relapse-free survival and overall survival. However, KIT and PDGFRA mutation are not completely responsible for the progression of disease, especially metastasis of GISTs. So, there could be other molecular mechanism in GISTs progression. ZEB1 (zinc finger E-box-binding homeobox 1), as a member in zinc finger and homeodomain transcriptional factor family, plays a key role in metastasis of some epithelial carcinomas, such as colorectal cancer, breast cancer and NSCLC. We present that ZEB1, as a vital molecular in epithelial-mesenchymal transition, could be a promising marker in predicting the prognosis in GISTs. Methods: Immunohistochemistry staining for paraffin-embedding slices from 157 patients firstly diagnosed as GIST is applied for detecting the ZEB1 expression. Clinical, pathological, molecular and survival time were analyzed. All performances were approved by the Medical Ethics Committee in the First Affiliated Hospital of Chongqing Medical University. Results: In 157 patients, metastasis was found in 87 patients. In 87 patients with metastasis, high expression of ZEB1 almost exhibited (80 high/96 VS 7 non or low/96), while non or low expression was frequently detected in patients without metastasis (50 non or low/70 VS 20 high/70) (p < 0.0001). There was no significant difference between high and non/low expression patients in gender (48% VS 46% for male rate; 52% VS 54% for female rate), age (53 vs 54 years for median age), primary location (esophagus 2% VS 1.8%; stomach 57% VS 52.6%; duodenum and small intestine 31% VS 31.6%; colorectum and anus 10% VS 14.0%), tumor size (0.5-24cm, median 9.7cm VS 1-25.5cm, median 10.1cm), mitotic index (55.0% VS 58.6% for > 5/50HPF; 45.0% VS 41.4% for ≤5/50HPF), and risk stratification (low/intermediate risk 60.7% VS 63%; high risk 39.3% VS 37%). In addition, the 5-year OS rate was considerably lower in patients with ZEB1 high expression than those with ZEB1 none or low expression at baseline (37% vs 86%; p = 0.011). Conclusions: High expression of ZEB1 facilitates metastasis and indicates the poor prognosis in GISTs. ZEB1 could be a novel predictor for GIST’s prognosis.