High expression of ZEB1 correlates with liver metastasis and poor prognosis in colorectal cancer

Abstract

Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to promote invasion and metastasis in several types of human cancer and to have a prognostic role in certain cancers. However, the clinical significance of ZEB1 in colorectal cancer (CRC) has not been sufficiently investigated. This study aimed to address this issue. In this study, we compared the expression of ZEB1 between CRC tissues and normal adjacent mucosa using quantitative real-time RT-PCR. The association of ZEB1 expression with clinicopathological characteristics was analyzed by appropriate statistical analyses. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the association of ZEB1 expression with survival of patients. The results showed that the relative expression levels of ZEB1 were significantly higher in CRC tissues compared to the normal adjacent mucosa and higher expression of ZEB1 correlated with liver metastasis. Kaplan-Meier analysis indicated that patients with high ZEB1 had a poor overall survival. Moreover, the multivariate analysis showed that high expression of ZEB1 was an independent predictor of overall survival. Our data indicate the potential of ZEB1 as a novel prognostic biomarker for CRC.

ZEB1: At the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance

“…5,[40][41][42] Due to the pivotal role of ZEB1 in the downregulation of E-cadherin, ZEB1 acts as a driver of EMT and cancer progression. 16,28,33,34,44 Aberrant expression of ZEB1 has been observed in many human cancers, such as uterine cancer, 45 pancreatic cancer, 29,46 osteosarcoma, 47 lung cancer, 48,49 liver cancer, 50 gastric cancer, 51,52 colon cancer 53 and breast cancer. 30 In these tumors, ZEB1 expression correlates with loss of E-cadherin and is associated with advanced diseases or metastasis, which indicates the relevance of ZEB1 induction of EMT and tumor progression in clinical cancers.…”

MSX1-Induced Neural Crest-Like Reprogramming Promotes Melanoma Progression

“…Our data suggest that the MSX1 regulatory network plays a critical role in the dynamic phenotypes of human melanomas and that blocking MSX1-driven reprogramming is sufficient to inhibit subsequent metastasis formation primarily in the liver. Precise mechanisms in MSX1-dependent liver metastasis still remain to be elucidated; however, several studies reported that high expression of ZEB1 and ZEB-induced mesenchymal phenotype is correlated with liver metastasis in several cancer types such as uveal melanoma and colorectal cancer (Chen et al, 2017; Spaderna et al, 2008; Zhang et al, 2013). Thus, it is plausible that the increased liver colonization is regulated by the MSX1-ZEB1 axis.…”

Clinical significance of zinc-finger E-box binding homeobox 1 mRNA levels in peritoneal washing for gastric cancer

“…ZEB1 is reportedly a key player in cancer progression (17,(30)(31)(32). In particular, high expression of ZEB1 in endometrial and colorectal cancers and hepatocellular carcinoma has been associated with poor prognosis (15,33,34). In gastric cancer, ZEB1 expression in cancer tissues has been identified as an independent prognostic factor (13,14).…”

“…Various transcription factors are known to trigger EMT (8)(9)(10), including zinc-finger E-box binding homeobox 1 (ZEB1), a central EMT mediator (11,12). ZEB1 reportedly affects cancer progression by regulating EMT in gastric, breast, prostate, ovarian and colorectal cancers (13)(14)(15)(16)(17)(18)(19)(20).…”