Znhit1 和 HIF-2α 与乳腺癌患者的癌症干细胞标志物相关。

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

机构信息

Department of Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.

Department of Cancer Management and Research, Medical Research Institute, Alexandria University, Alexandria, Egypt.

出版信息

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

DOI:10.1038/s41598-022-18133-8

PMID:35978075

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9385614/

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.

摘要

表观遗传改变已成为乳腺癌（BC）发生和发展的重要因素。缺氧肿瘤微环境调节乳腺癌干细胞（BCSCs）的干性表型。本研究旨在探讨 Znhit1 和 HIF-2α 基因在乳腺癌组织中的表达及其与 CSCs 标志物 LGR5、ALDH1A1 和 β-catenin 在 BC 患者组织和血清中的关系。本研究包括 160 名女性，分为两组，I 组：80 名健康女性作为对照组，II 组：80 名乳腺癌患者。通过 qRT-PCR 测定组织 Znhit1 和 HIF-2α 的基因表达。通过 ELISA 测定组织和血清 ALDH1A1、LGR5 和 β-catenin 水平。我们发现 Znhit1 的基因表达在 BC 组织中显著下调。此外，它与 BC 患者的临床分期和 β-catenin 水平呈显著负相关。关于 HIF-2α，HIF-2α 的基因表达在 BC 组织中显著上调。此外，它与 BC 患者的 Her-2/neu 表达和 β-catenin 水平呈显著正相关。根据我们的结果，Znhit1 和 HIF-2α 可能成为 BC 治疗的新的治疗靶点。此外，血清 ALDH1A1、LGR5 和 β-catenin 中的每一种都可能在非侵入性检测 BC 方面发挥重要作用，具有高特异性和敏感性。