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

Sci Rep. 2022 Aug 17;12(1):13918. doi: 10.1038/s41598-022-18133-8.

Abstract

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-2α gene expression in breast cancer tissues as well as their relation to CSCs markers LGR5, ALDH1A1 and β-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-2α was determined by qRT-PCR. Tissue and serum ALDH1A1, LGR5 and β-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 β-catenin levels in BC patients. Regarding HIF-2α, gene expression of HIF-2α was significantly upregulated in BC tissues. Moreover, it was significantly positively correlated with Her-2/neu expression and β-catenin levels in BC patients. Based upon our results, Znhit1 and HIF-2α may serve as novel therapeutic targets for BC therapy. Additionally, each of serum ALDH1A1, LGR5 and β-catenin may play a crucial role in non-invasive detection of BC with a high specificity and sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Hypoxia
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms* / pathology
  • Neoplastic Stem Cells / metabolism
  • Phosphoproteins / metabolism*
  • Tumor Microenvironment / genetics
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Phosphoproteins
  • ZNHIT1 protein, human
  • beta Catenin
  • endothelial PAS domain-containing protein 1