PKCζ, CTNNBIP1 and ALDH1A3 Expression in Luminal B Breast Cancer Indicates Decreased Hormone Therapy Effectiveness

The role of catenin β interacting protein 1 (CTNNBIP1), a negative regulator of the canonical Wnt/β-catenin signaling pathway, in luminal A and B breast cancer stem cells treated with hormone therapy is unknown. This study investigated the relationship between CTNNBIP1 and aldehyde dehydrogenase 1 family member A3 (ALDH1A3) expression and its impact on disease-specific survival in luminal A and B breast cancer. Given that high protein kinase ζ (PKCζ) expression, together with elevated CTNNBIP1 or ALDH1A3, is linked to poor prognosis in luminal B tumors, we also examined their combined influence.

Gene expression and clinical data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=2,509) were analyzed using Kaplan-Meier and Cox proportional hazards models. Findings were validated with The Cancer Genome Atlas Pan-Cancer Atlas (TCGA; n=1,084).

CTNNBIP1 ^high ALDH1A3 ^high indicated a poor prognosis in patients with luminal B breast cancer treated with hormone therapy in the METABRIC dataset and aromatase inhibitors as hormone therapy in the TCGA data set, suggesting that high CTNNBIP1 and ALDH1A3 expression contributed to decreased effectiveness of hormone therapy in patients with luminal B breast cancer. PKC ζ ^high CTNNBIP1 ^high ALDH1A3 ^high was associated with a poor prognosis in patients with luminal B breast cancer treated with hormone therapy and aromatase inhibitors, suggesting that high PKC ζ , CTNNBIP1 and ALDH1A3 expression contributed to decreased effectiveness of hormone therapy in patients with luminal B breast cancer.

PKC ζ and CTNNBIP1 may be involved in the progression of ALDH1A3-positive luminal B breast cancer. In luminal B breast cancer, PKC ζ , CTNNBIP1 and ALDH1A3 could serve as molecular drug targets and prognostic biomarkers to predict the effectiveness of hormone therapy.