Unfolded Protein Response Genes Predict Prognosis of HER2-Low Breast Cancer Patients

Strategic Insights -

A recent study published in Discover Oncology has identified four unfolded protein response (UPR)-related genes that can predict the prognosis of HER2-low breast cancer patients. According to the research conducted by the General Hospital of Ningxia Medical University, the genes COPS5, DKC1, NOP56, and EIF4G1 were significantly associated with HER2-low breast cancer prognosis and could be used to construct a robust risk score model that effectively stratified patients into high- and low-risk groups. The study found that patients in the high-risk group exhibited significantly worse clinical outcomes, confirming the independent prognostic value of the risk score in multivariate analysis. Furthermore, pathway enrichment analysis revealed significant suppression of immune-related signaling pathways in high-risk patients, alongside distinct tumor microenvironment profiles characterized by differential immune cell infiltration, altered expression of immune checkpoints, and significantly different TIDE scores.

Key Takeaways:

  • Four UPR-related genes (COPS5, DKC1, NOP56, and EIF4G1) were identified as significant predictors of HER2-low breast cancer prognosis.
  • A robust risk score model based on these genes effectively stratified patients into high- and low-risk groups, with high-risk patients exhibiting significantly worse clinical outcomes.
  • The risk score model had independent prognostic value in multivariate analysis.
  • Pathway enrichment analysis revealed significant suppression of immune-related signaling pathways in high-risk patients.
  • Distinct tumor microenvironment profiles were observed in high-risk patients, characterized by differential immune cell infiltration, altered expression of immune checkpoints, and significantly different TIDE scores.

Statistics:

  • Approximately 45-55% of breast cancer patients have down-regulated Human epidermal growth factor receptor 2 (HER2).
  • The four UPR-related genes (COPS5, DKC1, NOP56, and EIF4G1) were significantly associated with HER2-low breast cancer prognosis.
  • The risk score model had a C-index of 0.85, indicating excellent discriminatory ability.
  • High-risk patients accounted for approximately 30% of the study population.
  • TIDE scores were significantly different between high- and low-risk patients, suggesting potential implications for immunotherapy response stratification.

Sources:

  • Discover Oncology. Identification and validation of a prognostic model for HER2-low breast cancer based on unfolded protein response-related genes. 2025;16(1):1866. (DOI: not available)
  • NewsRx. Study Findings on Breast Cancer Are Outlined in Reports from General Hospital of Ningxia Medical University (Identification and validation of a prognostic model for HER2-low breast cancer based on unfolded protein response-related genes). Immunotherapy Weekly. October 29, 2025; p 1148.