A Novel Signature Based on Angiogenesis-Related Genes Predicts the Prognosis and Immunotherapy Response in HER2-Positive Breast Cancer.

Abstract

Background: HER2-positive breast cancer is one of the most prevalent subtypes of breast cancer and represents a significant health concern for women worldwide due to its high morbidity and mortality rates. Recent studies have consistently underscored the pivotal role of angiogenesis in the development and progression of HER2-positive breast cancer. Here, we developed a prognostic signature based on angiogenesis-related genes (ARGs) to categorize HER2-positive breast cancer patients and provide insights into their survival outcomes. Methods: Kaplan-Meier survival curve, time-dependent receiver operating characteristic (ROC) and nomogram were performed to investigate the prognostic performance of the signature. In addition, we comprehensively analyzed the correlation of the prognostic signature with immune cell infiltration, immune checkpoint inhibitors (ICIs) therapy. Finally, Immunohistochemistry (IHC) and immunoblotting were used to investigate XBP1 expression in HER2-positive breast cancer tissues. Colony formation assay was performed to examine cell proliferation of HER2-positive breast cancer cells. Results: The Kaplan-Meier curves and the ROC curves demonstrated that the ARGs had good performance in predicting the prognosis of HER2-positive breast cancer patients. In addition, we observed that the low-risk group was remarkably associated with immune infiltration and better response to ICIs. Further experimental results show that XBP1 is upregulated in human HER2-positive breast cancer, and its knockdown significantly inhibited cell proliferation. Conclusions: Our study demonstrated that the ARGs could serve as a novel biomarker for predicting the prognosis of patients with HER2-positive breast cancer and providing new insights into immunotherapy strategies for these patients.