Dual high expression of epithelial-mesenchymal transcription factors ZEB1 and ELF3 was inversely correlated with survival of liver cancer patients

Abstract

Liver cancer represents the sixth most prevalent form of cancer globally, with a markedly elevated mortality rate. Despite advancements in molecular diagnostics and therapies, only a few molecular markers are currently utilized in liver cancer diagnosis and treatment. The epithelial-mesenchymal transition (EMT) is a pivotal process during embryonic development and is also observed in pathological contexts such as cancer progression. Mesenchymal- epithelial transition (MET) represents the reverse process of EMT. Recent studies have demonstrated that cancer cells exhibit heightened aggressiveness when they acquire a hybrid epithelial/mesenchymal phenotype. Major transcription factors regulate EMT and MET processes. This study examined the expression of EMT-inducing transcription factors (ZEB1, TWIST, SNAI1) and MET-inducing transcription factors (GRHL2, ELF3, OVOL1) to gain insight into hybrid epithelial/mesenchymal states in liver cancer. A strong positive correlation was observed between ZEB1 and ELF3, as well as SNAI1 and GRHL2 gene expressions. Protein analyses revealed the highest correlation between ZEB1 and ELF3. Furthermore, high- expression groups of ZEB1 and ELF3 were associated with significantly lower survival rates compared to low-expression groups. These findings suggest that dual expression of ZEB1 and ELF3 could serve as a potential diagnostic marker in liver cancer.