SIX4, a potential therapeutic target for estrogen receptor-positive breast cancer patients, is associated with low promoter methylation level

Epigenomics. 2023 Sep;15(18):911-925. doi: 10.2217/epi-2023-0232. Epub 2023 Oct 31.

Abstract

Aim: To investigate SIX4 in breast cancer. Methods: Publicly available online tools were used to analyze the expression, methylation and prognostic significance of SIX4 in breast cancer, as well as its immunohistochemistry. Results: High SIX4 levels were associated with low SIX4 promoter methylation, especially in estrogen receptor-positive breast cancer. Increased SIX4 was related to advanced stage and decreased immune infiltration. Gene set enrichment analysis found that the SIX4-correlated genes were enriched in transcriptional processing and immune response. Patients with high SIX4 expression tended to have poor survival, especially those with estrogen receptor-positive breast cancer. Conclusion: High SIX4 expression in breast cancer plays an oncogenic role, promoting the development of malignancies through suppressing the immune response, especially in luminal subtypes, and is associated with a low promoter methylation level.

Keywords: SIX4; breast cancer; immune response; methylation; stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • DNA Methylation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Homeobox
  • Homeodomain Proteins / genetics
  • Humans
  • Prognosis
  • Promoter Regions, Genetic
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Trans-Activators / genetics

Substances

  • Receptors, Estrogen
  • SIX4 protein, human
  • Trans-Activators
  • Homeodomain Proteins