Background: YAP1, an oncogene in numerous cancers, is a downstream transcription factor of the Hippo pathway. This study focuses on its relationship with the Oncotype Dx (ODX) test risk score (RS) in patients with hormone-receptor-positive, HER2-negative (HR+HER2−) breast cancer. Methods: We retrospectively analyzed 401 HR+HER2− breast cancer patients from Gangnam Severance Hospital who underwent ODX tests (May 2014–April 2020). YAP1 nuclear localization was evaluated via immunohistochemical staining and its clinical correlation with clinicopathological parameters, including RS, was analyzed. Public datasets TCGA-BRCA and METABRIC validated clinical outcomes. Results: YAP1 expression negatively correlated with ODX RS (OR 0.373,p= 0.002). Elevated YAP1 mRNA levels corresponded to better clinical outcomes, specifically in ER-positive patients, with significant results in METABRIC and TCGA-BRCA datasets (p< 0.0001 OS in METABRIC,p= 0.00085 RFS in METABRIC,p= 0.040 DFS in TCGA-BRCA). In subsets with varying ESR1 mRNA expression and pronounced YAP1 expression, superior survival outcomes were consistently observed. Conclusion: YAP1 may be a valuable prognostic marker and potential therapeutic target in HR+HER2− breast cancer patients.
背景：YAP1作为多种癌症中的一种癌基因，是Hippo通路的下游转录因子。本研究聚焦于其在激素受体阳性、HER2阴性（HR+HER2−）乳腺癌患者中与Oncotype Dx（ODX）检测风险评分（RS）的关系。方法：我们回顾性分析了来自江南Severance医院的401例HR+HER2−乳腺癌患者（2014年5月至2020年4月），这些患者均接受了ODX检测。通过免疫组织化学染色评估YAP1核定位，并分析其与临床病理参数（包括RS）的临床相关性。公共数据集TCGA-BRCA和METABRIC验证了临床结果。结果：YAP1表达与ODX RS呈负相关（OR 0.373，p=0.002）。YAP1 mRNA水平升高与更好的临床结局相关，特别是在ER阳性患者中，METABRIC和TCGA-BRCA数据集均显示显著结果（METABRIC中OS p<0.0001，RFS p=0.00085；TCGA-BRCA中DFS p=0.040）。在不同ESR1 mRNA表达水平且YAP1表达显著的亚组中，均观察到更优的生存结局。结论：YAP1可能是HR+HER2−乳腺癌患者有价值的预后标志物和潜在治疗靶点。
肿瘤(癌症)患者之家