Prognostic significance of ZEB1 and ZEB2 in digestive cancers: a cohort-based analysis and secondary analysis

BACKGROUND Digestive cancers are common malignancies worldwide, however there are few effective prognostic markers available. In this study we comprehensively investigated the prognostic significance of ZEB1 and ZEB2 in digestive cancers. METHODS Electronic databases were searched and studies met the selection criteria were included. Study information was recorded and quality assessment was performed according to the REMARK guideline. Hazard ratios and its corresponding 95% confidence intervals were extracted and pooled. Sensitivity analyses, subgroup analyses, cumulative meta-analyses and secondary analyses were also performed to increase the stability and reliability of our results. RESULTS 24 cohort studies were included in the study. High ZEB1 and ZEB2 levels predicted poor overall survival, meanwhile high ZEB2 levels predicted poor disease free survival for digestive cancer patients. From subgroup analyses we observed ZEB1 was found to be significantly associated with poor overall survival for patients with pancreatic cancer, gastric cancer and colorectal cancer, while ZEB2 was found to be significantly associated with poor overall survival for patients with hepatocellular carcinoma and gastric cancer. Furthermore, by conducting secondary analyses we confirmed both ZEB1 and ZEB2 played important roles in gastric cancer prediction. In addition, we found high ZEB1 and ZEB2 expression were significantly associated with depth of invasion, lymph node metastasis and TNM stage in digestive cancer patients. CONCLUSIONS The present study validated the prognostic value and clinicopathological association of ZEB1 and ZEB2 in digestive cancers, especially in gastric cancer.