Abstract

Background/Objectives: PgRMC1 is a progesterone-binding protein often overexpressed in breast cancer, correlating with tumor progression and chemoresistance. Identifying predictive markers for neoadjuvant chemotherapy (NAC) response is crucial for guiding therapeutic decisions. This study examines PgRMC1 expression in breast cancer tissues and its correlation with clinicopathological characteristics and NAC response. Methods: PgRMC1 expression in normal and cancerous breast tissues was evaluated via immunohistochemistry (IHC). Expression of ER, PgR, HER2, AR, and PGRMC1 mRNA was determined by qPCR in 112 patients. A separate 44-patient neoadjuvant chemotherapy (NAC) cohort was assessed for intrinsic subtypes (pretreatment biopsies) alongside PgRMC1 IHC expression and pathological response (post-NAC surgical specimens). In vitro chemoresistance and qPCR analyses were performed in breast cancer cell lines following PgRMC1 overexpression or siRNA-mediated knockdown. Results: PgRMC1 expression was detected in breast cancer tissue, while no immunoreactivity was observed in normal breast tissue. PGRMC1 mRNA expression levels were significantly higher in luminal and HER2 subtypes. In the distinct cohort of patients treated with NAC, those with a poorer pathological response had significantly higher PgRMC1 expression than those with a good response. In vitro, forced overexpression of PgRMC1 in two breast cancer cell lines, MCF7 and MDA-MB-468, significantly reduced chemosensitivity. Overexpression of PgRMC1 modulated the expression of epithelial and differentiation markers, including CDH1, AR, KRT19, and GATA3. Conclusions: PgRMC1 may contribute to chemoresistance and serves as a candidate biomarker for assessing neoadjuvant chemotherapy sensitivity.

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