High Expression of CD58 and ALDH1A3 Predicts a Poor Prognosis in Basal-like Breast Cancer

Anticancer Res. 2022 Nov;42(11):5223-5232. doi: 10.21873/anticanres.16029.

Abstract

Background/aim: CD58 is an immune adhesion molecule on the cellular surface. It was previously found that a high expression of CD58 predicted a poor prognosis of patients with lower-grade gliomas. Therefore, the aim of this paper was to investigate the association between CD58 and breast cancer.

Materials and methods: CD58 gene expression data downloaded from cBioPortal was compared between the different subtypes of breast cancer. Clinical prognosis was examined using Kaplan-Meier analysis and multivariable Cox regression analysis. The association between CD58 expression and immune cell infiltration was estimated using the TIMER 2.0 web platform. Finally, the tumour sphere formation of aldehyde dehydrogenase 1 (ALDH1)high basal-like breast cancer stem cells in which CD58 was knocked down using siRNA was measured.

Results: CD58 mRNA was mainly enriched in claudin-low and basal-like subtypes. The high expression of CD58 predicted a good prognosis in patients with luminal A and luminal B breast cancer. This prediction may be due to the association of immune cell infiltration with CD58. Notably, patients with luminal A breast cancer with a high expression of CD58 in association with ALDH1A3 exhibited a good prognosis; however, this did not apply to patients with basal-like breast cancer. The in vitro experiments revealed that knockdown of CD58 inhibited the tumour sphere formation ability of ALDH1high basal-like cancer cells.

Conclusion: CD58 may function as a potential prognostic biomarker and therapeutic target in ALDH-positive basal-like cancer stem cells.

Keywords: ALDH1; Breast cancer; CD58; basal-like; cancer stem cell; luminal; prognostic marker.

MeSH terms

  • Aldehyde Dehydrogenase 1 Family
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / pathology
  • CD58 Antigens / metabolism
  • Claudins
  • Female
  • Humans
  • Prognosis
  • RNA, Messenger
  • RNA, Small Interfering
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism

Substances

  • Aldehyde Dehydrogenase 1 Family
  • Biomarkers, Tumor
  • Claudins
  • Retinal Dehydrogenase
  • RNA, Messenger
  • RNA, Small Interfering
  • CD58 Antigens
  • aldehyde dehydrogenase (NAD(P)+)