Gene Expression and Prognostic Value of NADPH Oxidase Enzymes in Breast Cancer

Int J Mol Sci. 2024 Mar 19;25(6):3464. doi: 10.3390/ijms25063464.

Abstract

NADPH oxidase enzymes (NOX) are involved in all stages of carcinogenesis, but their expression levels and prognostic value in breast cancer (BC) remain unclear. Thus, we aimed to assess the expression and prognostic value of NOX enzymes in BC samples using online databases. For this, mRNA expression from 290 normal breast tissue samples and 1904 BC samples obtained from studies on cBioPortal, Kaplan-Meier Plotter, and The Human Protein Atlas were analyzed. We found higher levels of NOX2, NOX4, and Dual oxidase 1 (DUOX1) in normal breast tissue. NOX1, NOX2, and NOX4 exhibited higher expression in BC, except for the basal subtype, where NOX4 expression was lower. DUOX1 mRNA levels were lower in all BC subtypes. NOX2, NOX4, and NOX5 mRNA levels increased with tumor progression stages, while NOX1 and DUOX1 expression decreased in more advanced stages. Moreover, patients with low expression of NOX1, NOX4, and DUOX1 had lower survival rates than those with high expression of these enzymes. In conclusion, our data suggest an overexpression of NOX enzymes in breast cancer, with certain isoforms showing a positive correlation with tumor progression.

Keywords: NADPH oxidases; breast cancer; reactive oxygen species; tumor aggressiveness.

MeSH terms

  • Breast Neoplasms* / genetics
  • Dual Oxidases / genetics
  • Female
  • Gene Expression
  • Humans
  • NADPH Oxidase 1 / genetics
  • NADPH Oxidase 4 / genetics
  • NADPH Oxidases* / genetics
  • NADPH Oxidases* / metabolism
  • Prognosis
  • RNA, Messenger / genetics
  • Reactive Oxygen Species / metabolism

Substances

  • NADPH Oxidases
  • Dual Oxidases
  • Reactive Oxygen Species
  • RNA, Messenger
  • NADPH Oxidase 4
  • NADPH Oxidase 1