EMP3 Expression in HER2-Enriched Breast Cancer is Linked to PI3K/AKT Signaling and Indicates Poor Prognosis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• HER2-enriched breast cancer is a distinct subtype often treated with trastuzumab.
• Trastuzumab resistance is a significant clinical challenge in HER2-positive breast cancer.
• The role of EMP3 in predicting prognosis and treatment response in HER2-enriched breast cancer requires further investigation.

Purpose of the Study:

• To investigate the prognostic value of EMP3 expression in HER2-enriched breast cancer.
• To clarify the relationship between EMP3 expression and trastuzumab resistance.
• To explore the underlying molecular mechanisms involving the PI3K-AKT pathway.

Main Methods:

• Immunohistochemistry was used to assess EMP3 expression in 90 HER2-enriched breast cancer patients.
• Cox regression analysis and nomogram construction were employed to identify independent prognostic factors for disease-free survival (DFS).
• Gene expression analysis, pathway mapping (KEGG), in vitro cell assays, and in vivo xenograft models were utilized to study EMP3's role in trastuzumab resistance and the PI3K-AKT pathway.

Main Results:

• EMP3 expression was identified as an independent prognostic factor for DFS in HER2-enriched breast cancer.
• A prognostic model incorporating EMP3, T-stage, and N-stage demonstrated good predictive power (C-index: 0.745).
• High EMP3 expression correlated with enhanced PI3K-AKT pathway activation and was associated with trastuzumab resistance, as confirmed by in vitro and in vivo experiments.

Conclusions:

• Elevated EMP3 expression is a predictor of poor outcomes in HER2-enriched breast cancer.
• EMP3 overexpression upregulates the PI3K-AKT pathway, promoting the development of trastuzumab resistance.
• Targeting EMP3 or the PI3K-AKT pathway may offer therapeutic strategies to overcome trastuzumab resistance.