Chen Shuanglong, Cui Weiheng, Dong Jiale, Chen Wenyan, Dong Hongmei, Zhao Ruijun
Institute of Precision Cancer Medicine and Pathology, and Department of Pathology, School of Medicine, Jinan University, Guangzhou, China.
School of Nursing and Rehabilitation, Xi'an FANYI University, Xian, China.
J Cancer. 2024 Jul 8;15(14):4731-4748. doi: 10.7150/jca.94120. eCollection 2024.
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. 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. 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. 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.
人表皮生长因子受体2（HER2）阳性乳腺癌是最常见的乳腺癌亚型之一，因其高发病率和死亡率，对全球女性的健康构成重大威胁。最近的研究一致强调血管生成在HER2阳性乳腺癌发生和发展中的关键作用。在此，我们基于血管生成相关基因（ARG）开发了一种预后特征，用于对HER2阳性乳腺癌患者进行分类，并深入了解其生存结果。采用Kaplan-Meier生存曲线、时间依赖性受试者工作特征（ROC）曲线和列线图来研究该特征的预后性能。此外，我们全面分析了预后特征与免疫细胞浸润、免疫检查点抑制剂（ICI）治疗的相关性。最后，采用免疫组织化学（IHC）和免疫印迹法研究XBP1在HER2阳性乳腺癌组织中的表达。进行集落形成试验以检测HER2阳性乳腺癌细胞的增殖情况。Kaplan-Meier曲线和ROC曲线表明，ARG在预测HER2阳性乳腺癌患者的预后方面具有良好的性能。此外，我们观察到低风险组与免疫浸润显著相关，对ICI的反应更好。进一步的实验结果表明，XBP1在人HER2阳性乳腺癌中上调，其敲低显著抑制细胞增殖。我们的研究表明，ARG可作为预测HER2阳性乳腺癌患者预后的新型生物标志物，并为这些患者的免疫治疗策略提供新的见解。
