Analysis of Endoplasmic Reticulum Stress-Associated Proteins As Prognostic Markers In Breast Cancer

Introduction: Breast cancer is a complex, heterogeneous disease that poses a significant global health risk. Both internal and external cellular stresses contribute to breast cancer progression. Endoplasmic reticulum (ER) stress is one such cellular stress response that activates intricate intracellular signaling pathways collectively known as the unfolded protein response (UPR). Maintaining protein homeostasis and regulating these pathways is essential in breast cancer progression. Methods: Using STRING and Harmonizome Reactome pathway datasets, we identified a list of UPR-associated genes. The Human Protein Atlas and UALCAN databases were used to analyze these genes as potential prognostic markers in breast cancer. Results: Three prognostic markers were identified in patients with breast cancer: FK506 binding protein 14 (FKBP14), S-phase kinase-associated protein 1 (SKP1), and Baculoviral IAP repeat containing 3 (BIRC3). Discussion: Expression levels of FKBP14, SKP1, and BIRC3 were compared to TCGA normal and GTEx data using the GEPIA2 database. Our analysis indicates that higher SKP1 expression is associated with poor overall survival and prognosis, whereas higher BIRC3 expression correlates with better prognosis and overall survival. BIRC3 protein levels are elevated in tumor tissue and increase as the tumor progresses through various stages. Additionally, the expression of these markers varies according to sex, age, ethnicity, breast cancer subtype, nodal metastasis, and menopause status. Conclusion: Overall, our study identifies that the genes involved in ER stress that are associated with breast cancer can serve as prognostic markers.