Znhit1 and HIF-2α are correlated with cancer stem cell markers in breast cancer patients

Epigenetic alterations have emerged as fundamental players in development and progression of breast cancer (BC). A hypoxic tumour microenvironment regulates the stemness phenotype in breast cancer stem cells (BCSCs). The aim of this study was to investigate Znhit1 and HIF-2 alpha gene expression in breast cancer tissues as well as their relation to CSCs markers LGR5, ALDH1A1 and beta-catenin in tissue and serum of BC patients. The present study included 160 females divided into two groups, group I: 80 healthy females served as control group and group II: 80 breast cancer patients. Gene expression of tissue Znhit1 and HIF-2 alpha was determined by qRT-PCR. Tissue and serum ALDH1A1, LGR5 and beta-catenin levels were determined by ELISA. We found that gene expression of Znhit1 was significantly downregulated in BC tissues. Moreover, it was significantly negatively correlated with clinical stage and beta-catenin levels in BC patients. Regarding HIF-2 alpha, gene expression of HIF-2 alpha was significantly upregulated in BC tissues. Moreover, it was significantly positively correlated with Her-2/neu expression and beta-catenin levels in BC patients. Based upon our results, Znhit1 and HIF-2 alpha may serve as novel therapeutic targets for BC therapy. Additionally, each of serum ALDH1A1, LGR5 and beta-catenin may play a crucial role in non-invasive detection of BC with a high specificity and sensitivity.