Luminal B Breast Cancer Coexpressing p62 and ALDH1A3 Is Less Susceptible to Radiotherapy.

Background/aim: We have reported that p62 (also known as sequestosome 1) is needed for survival/proliferation and tumor formation by aldehyde dehydrogenase 1 (ALDH1) -positive cancer stem cells (CSCs) and that p62 ^high ALDH1A3 ^high expression is associated with a poor prognosis in luminal B breast cancer. However, the association between p62 ^high ALDH1A3 ^high and the benefit from radiotherapy in patients with luminal B breast cancer remains unclear.
Materials and Methods: Datasets from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) were downloaded, and data from p62 ^high ALDH1A3 ^high luminal B patients treated without or with radiotherapy were analyzed by Kaplan-Meier and multivariate Cox regression analyses. We also performed an in vitro tumor sphere formation assay after X-ray irradiation using p62-knockdown ALDH1 ^high luminal B BT-474 cells.
Results: p62 ^high ALDH1A3 ^high patients had poorer clinical outcomes than other luminal B breast cancer patients treated with radiotherapy. The combination of p62 DsiRNA KD and X-ray irradiation suppressed in vitro tumor sphere formation by ALDH1 ^high BT-474 cells. These results suggest that p62 is involved in the reduced effect of X-ray irradiation on ALDH1-positive luminal B breast CSCs.
Conclusion: p62 and ALDH1A3 may serve as prognostic biomarkers for luminal B breast cancer patients treated with radiotherapy. Additionally, the combination of p62 inhibition and radiotherapy could be useful for targeted strategies against ALDH1-positive luminal B breast CSCs.
(Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)